Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox.

PubMed

Lavie, Carl J; McAuley, Paul A; Church, Timothy S; Milani, Richard V; Blair, Steven N

2014-04-15

Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Obesity, metabolic dysfunction and cardiac fibrosis: pathophysiologic pathways, molecular mechanisms and therapeutic opportunities

PubMed Central

Cavalera, Michele; Wang, Junhong; Frangogiannis, Nikolaos G

2014-01-01

Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients. PMID:24880146

Therapeutic alliance and obesity management in primary care - a cross-sectional pilot using the Working Alliance Inventory.

PubMed

Sturgiss, E A; Sargent, G M; Haesler, E; Rieger, E; Douglas, K

2016-12-01

Therapeutic alliance is a well-recognized predictor of patient outcomes within psychological therapy. It has not been applied to obesity interventions, and Bordin's theoretical framework shows particular relevance to the management of obesity in primary health care. This cross-sectional study of a weight management programme in general practice aimed to determine if therapeutic alliance was associated with patient outcomes. The Working Alliance Inventory short revised version (WAI-SR) was administered to 23 patients and 11 general practitioners (GPs) at the end of a 6-month weight management programme. Use of the WAI-SR indicated that the strength of therapeutic alliance varied between different patient-GP relationships in this pilot intervention. A robust therapeutic alliance was strongly associated with patient engagement in the weight management programme indicated by number of appointments. It was also associated with some general health and quality of life outcomes. These are promising results that require confirmation with larger studies in primary health care. The measurement of therapeutic alliance using the WAI-SR may predict patient attendance and outcomes in obesity interventions in primary healthcare settings. © 2016 World Obesity Federation.

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

PubMed

Turcot, Valérie; Lu, Yingchang; Highland, Heather M; Schurmann, Claudia; Justice, Anne E; Fine, Rebecca S; Bradfield, Jonathan P; Esko, Tõnu; Giri, Ayush; Graff, Mariaelisa; Guo, Xiuqing; Hendricks, Audrey E; Karaderi, Tugce; Lempradl, Adelheid; Locke, Adam E; Mahajan, Anubha; Marouli, Eirini; Sivapalaratnam, Suthesh; Young, Kristin L; Alfred, Tamuno; Feitosa, Mary F; Masca, Nicholas G D; Manning, Alisa K; Medina-Gomez, Carolina; Mudgal, Poorva; Ng, Maggie C Y; Reiner, Alex P; Vedantam, Sailaja; Willems, Sara M; Winkler, Thomas W; Abecasis, Gonçalo; Aben, Katja K; Alam, Dewan S; Alharthi, Sameer E; Allison, Matthew; Amouyel, Philippe; Asselbergs, Folkert W; Auer, Paul L; Balkau, Beverley; Bang, Lia E; Barroso, Inês; Bastarache, Lisa; Benn, Marianne; Bergmann, Sven; Bielak, Lawrence F; Blüher, Matthias; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Böger, Carsten A; Bork-Jensen, Jette; Bots, Michiel L; Bottinger, Erwin P; Bowden, Donald W; Brandslund, Ivan; Breen, Gerome; Brilliant, Murray H; Broer, Linda; Brumat, Marco; Burt, Amber A; Butterworth, Adam S; Campbell, Peter T; Cappellani, Stefania; Carey, David J; Catamo, Eulalia; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der I; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Cocca, Massimiliano; Collins, Francis S; Cook, James P; Corley, Janie; Corominas Galbany, Jordi; Cox, Amanda J; Crosslin, David S; Cuellar-Partida, Gabriel; D'Eustacchio, Angela; Danesh, John; Davies, Gail; Bakker, Paul I W; Groot, Mark C H; Mutsert, Renée; Deary, Ian J; Dedoussis, George; Demerath, Ellen W; Heijer, Martin; Hollander, Anneke I; Ruijter, Hester M; Dennis, Joe G; Denny, Josh C; Di Angelantonio, Emanuele; Drenos, Fotios; Du, Mengmeng; Dubé, Marie-Pierre; Dunning, Alison M; Easton, Douglas F; Edwards, Todd L; Ellinghaus, David; Ellinor, Patrick T; Elliott, Paul; Evangelou, Evangelos; Farmaki, Aliki-Eleni; Farooqi, I Sadaf; Faul, Jessica D; Fauser, Sascha; Feng, Shuang; Ferrannini, Ele; Ferrieres, Jean; Florez, Jose C; Ford, Ian; Fornage, Myriam; Franco, Oscar H; Franke, Andre; Franks, Paul W; Friedrich, Nele; Frikke-Schmidt, Ruth; Galesloot, Tessel E; Gan, Wei; Gandin, Ilaria; Gasparini, Paolo; Gibson, Jane; Giedraitis, Vilmantas; Gjesing, Anette P; Gordon-Larsen, Penny; Gorski, Mathias; Grabe, Hans-Jörgen; Grant, Struan F A; Grarup, Niels; Griffiths, Helen L; Grove, Megan L; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeff; Hakonarson, Hakon; Hammerschlag, Anke R; Hansen, Torben; Harris, Kathleen Mullan; Harris, Tamara B; Hattersley, Andrew T; Have, Christian T; Hayward, Caroline; He, Liang; Heard-Costa, Nancy L; Heath, Andrew C; Heid, Iris M; Helgeland, Øyvind; Hernesniemi, Jussi; Hewitt, Alex W; Holmen, Oddgeir L; Hovingh, G Kees; Howson, Joanna M M; Hu, Yao; Huang, Paul L; Huffman, Jennifer E; Ikram, M Arfan; Ingelsson, Erik; Jackson, Anne U; Jansson, Jan-Håkan; Jarvik, Gail P; Jensen, Gorm B; Jia, Yucheng; Johansson, Stefan; Jørgensen, Marit E; Jørgensen, Torben; Jukema, J Wouter; Kahali, Bratati; Kahn, René S; Kähönen, Mika; Kamstrup, Pia R; Kanoni, Stavroula; Kaprio, Jaakko; Karaleftheri, Maria; Kardia, Sharon L R; Karpe, Fredrik; Kathiresan, Sekar; Kee, Frank; Kiemeney, Lambertus A; Kim, Eric; Kitajima, Hidetoshi; Komulainen, Pirjo; Kooner, Jaspal S; Kooperberg, Charles; Korhonen, Tellervo; Kovacs, Peter; Kuivaniemi, Helena; Kutalik, Zoltán; Kuulasmaa, Kari; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A; Lamparter, David; Lange, Ethan M; Lange, Leslie A; Langenberg, Claudia; Larson, Eric B; Lee, Nanette R; Lehtimäki, Terho; Lewis, Cora E; Li, Huaixing; Li, Jin; Li-Gao, Ruifang; Lin, Honghuang; Lin, Keng-Hung; Lin, Li-An; Lin, Xu; Lind, Lars; Lindström, Jaana; Linneberg, Allan; Liu, Ching-Ti; Liu, Dajiang J; Liu, Yongmei; Lo, Ken S; Lophatananon, Artitaya; Lotery, Andrew J; Loukola, Anu; Luan, Jian'an; Lubitz, Steven A; Lyytikäinen, Leo-Pekka; Männistö, Satu; Marenne, Gaëlle; Mazul, Angela L; McCarthy, Mark I; McKean-Cowdin, Roberta; Medland, Sarah E; Meidtner, Karina; Milani, Lili; Mistry, Vanisha; Mitchell, Paul; Mohlke, Karen L; Moilanen, Leena; Moitry, Marie; Montgomery, Grant W; Mook-Kanamori, Dennis O; Moore, Carmel; Mori, Trevor A; Morris, Andrew D; Morris, Andrew P; Müller-Nurasyid, Martina; Munroe, Patricia B; Nalls, Mike A; Narisu, Narisu; Nelson, Christopher P; Neville, Matt; Nielsen, Sune F; Nikus, Kjell; Njølstad, Pål R; Nordestgaard, Børge G; Nyholt, Dale R; O'Connel, Jeffrey R; O'Donoghue, Michelle L; Olde Loohuis, Loes M; Ophoff, Roel A; Owen, Katharine R; Packard, Chris J; Padmanabhan, Sandosh; Palmer, Colin N A; Palmer, Nicholette D; Pasterkamp, Gerard; Patel, Aniruddh P; Pattie, Alison; Pedersen, Oluf; Peissig, Peggy L; Peloso, Gina M; Pennell, Craig E; Perola, Markus; Perry, James A; Perry, John R B; Pers, Tune H; Person, Thomas N; Peters, Annette; Petersen, Eva R B; Peyser, Patricia A; Pirie, Ailith; Polasek, Ozren; Polderman, Tinca J; Puolijoki, Hannu; Raitakari, Olli T; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F; Renström, Frida; Rheinberger, Myriam; Ridker, Paul M; Rioux, John D; Rivas, Manuel A; Roberts, David J; Robertson, Neil R; Robino, Antonietta; Rolandsson, Olov; Rudan, Igor; Ruth, Katherine S; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J; Sapkota, Yadav; Sattar, Naveed; Schoen, Robert E; Schreiner, Pamela J; Schulze, Matthias B; Scott, Robert A; Segura-Lepe, Marcelo P; Shah, Svati H; Sheu, Wayne H-H; Sim, Xueling; Slater, Andrew J; Small, Kerrin S; Smith, Albert V; Southam, Lorraine; Spector, Timothy D; Speliotes, Elizabeth K; Starr, John M; Stefansson, Kari; Steinthorsdottir, Valgerdur; Stirrups, Kathleen E; Strauch, Konstantin; Stringham, Heather M; Stumvoll, Michael; Sun, Liang; Surendran, Praveen; Swift, Amy J; Tada, Hayato; Tansey, Katherine E; Tardif, Jean-Claude; Taylor, Kent D; Teumer, Alexander; Thompson, Deborah J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Thuesen, Betina H; Tönjes, Anke; Tromp, Gerard; Trompet, Stella; Tsafantakis, Emmanouil; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tyrer, Jonathan P; Uher, Rudolf; Uitterlinden, André G; Uusitupa, Matti; Laan, Sander W; Duijn, Cornelia M; Leeuwen, Nienke; van Setten, Jessica; Vanhala, Mauno; Varbo, Anette; Varga, Tibor V; Varma, Rohit; Velez Edwards, Digna R; Vermeulen, Sita H; Veronesi, Giovanni; Vestergaard, Henrik; Vitart, Veronique; Vogt, Thomas F; Völker, Uwe; Vuckovic, Dragana; Wagenknecht, Lynne E; Walker, Mark; Wallentin, Lars; Wang, Feijie; Wang, Carol A; Wang, Shuai; Wang, Yiqin; Ware, Erin B; Wareham, Nicholas J; Warren, Helen R; Waterworth, Dawn M; Wessel, Jennifer; White, Harvey D; Willer, Cristen J; Wilson, James G; Witte, Daniel R; Wood, Andrew R; Wu, Ying; Yaghootkar, Hanieh; Yao, Jie; Yao, Pang; Yerges-Armstrong, Laura M; Young, Robin; Zeggini, Eleftheria; Zhan, Xiaowei; Zhang, Weihua; Zhao, Jing Hua; Zhao, Wei; Zhao, Wei; Zhou, Wei; Zondervan, Krina T; Rotter, Jerome I; Pospisilik, John A; Rivadeneira, Fernando; Borecki, Ingrid B; Deloukas, Panos; Frayling, Timothy M; Lettre, Guillaume; North, Kari E; Lindgren, Cecilia M; Hirschhorn, Joel N; Loos, Ruth J F

2018-01-01

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

The obesity epidemic: implications for recruitment and retention of defence force personnel.

PubMed

McLaughlin, R; Wittert, G

2009-11-01

The primary purpose of fitness and body composition standards in the military has always been to select individuals best suited to the physical demands of military service. Obesity has reached epidemic proportions globally, and may have adverse consequences for the military: a worsening prevalence of obesity in young civilian adults could hinder the recruitment and maintenance of military manpower. This review explores the impact of obesity on suitability for employment in defence force careers and any potential impact on long-term occupational health. Studies containing data on obesity and the military were identified from an electronic database. Thirty-eight papers were identified and 17 were included in this review. There is a limited body of evidence available to ascertain whether or not obese individuals are suitable for employment in the military. There are a number of key issues that need to be addressed before a definitive conclusion can be drawn. These include the future health of obese personnel recruited into the military and subsequent implications for health services, costs to the organization and military readiness, and the ability of an obese person to be an active member of the military workforce. Future research should be targeted towards these areas in order to determine the implications of obesity for recruitment and retention of defence force personnel.

Opposing tissue-specific roles of angiotensin in the pathogenesis of obesity, and implications for obesity-related hypertension

PubMed Central

Littlejohn, Nicole K.

2015-01-01

Metabolic disease, specifically obesity, has now become the greatest challenge to improving cardiovascular health. The renin-angiotensin system (RAS) exists as both a circulating hormone system and as a local paracrine signaling mechanism within various tissues including the brain, kidney, and adipose, and this system is strongly implicated in cardiovascular health and disease. Growing evidence also implicates the RAS in the control of energy balance, supporting the concept that the RAS may be mechanistically involved in the pathogenesis of obesity and obesity hypertension. Here, we review the involvement of the RAS in the entire spectrum of whole organism energy balance mechanisms, including behaviors (food ingestion and spontaneous physical activity) and biological processes (digestive efficiency and both aerobic and nonaerobic resting metabolic rates). We hypothesize that opposing, tissue-specific effects of the RAS to modulate these various components of energy balance can explain the apparently paradoxical results reported by energy-balance studies that involve stimulating, versus disrupting, the RAS. We propose a model in which such opposing and tissue-specific effects of the RAS can explain the failure of simple, global RAS blockade to result in weight loss in humans, and hypothesize that obesity-mediated uncoupling of endogenous metabolic rate control mechanisms can explain the phenomenon of obesity-related hypertension. PMID:26491099

Functional Imaging for Prostate Cancer: Therapeutic Implications

PubMed Central

Aparici, Carina Mari; Seo, Youngho

2012-01-01

Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

The Vicious Cycle of Myostatin Signaling in Sarcopenic Obesity: Myostatin Role in Skeletal Muscle Growth, Insulin Signaling and Implications for Clinical Trials.

PubMed

Consitt, L A; Clark, B C

2018-01-01

The age-related loss of skeletal muscle (sarcopenia) is a major health concern as it is associated with physical disability, metabolic impairments, and increased mortality. The coexistence of sarcopenia with obesity, termed 'sarcopenic obesity', contributes to skeletal muscle insulin resistance and the development of type 2 diabetes, a disease prevalent with advancing age. Despite this knowledge, the mechanisms contributing to sarcopenic obesity remain poorly understood, preventing the development of targeted therapeutics. This article will discuss the clinical and physiological consequences of sarcopenic obesity and propose myostatin as a potential candidate contributing to this condition. A special emphasis will be placed on examining the role of myostatin signaling in impairing both skeletal muscle growth and insulin signaling. In addition, the role of myostatin in regulating muscle-to fat cross talk, further exacerbating metabolic dysfunction in the elderly, will be highlighted. Lastly, we discuss how this knowledge has implications for the design of myostatin-inhibitor clinical trials.

Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity.

PubMed

Chen, Zhongyi; Guo, Lilu; Zhang, Yongqin; Walzem, Rosemary L; Pendergast, Julie S; Printz, Richard L; Morris, Lindsey C; Matafonova, Elena; Stien, Xavier; Kang, Li; Coulon, Denis; McGuinness, Owen P; Niswender, Kevin D; Davies, Sean S

2014-08-01

Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gut microbiota composition is a contributing factor to the susceptibility of an individual to the development of these disorders; therefore, altering a person's microbiota may ameliorate disease. One potential microbiome-altering strategy is the incorporation of modified bacteria that express therapeutic factors into the gut microbiota. For example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the N-acylethanolamide (NAE) family of lipids, which are synthesized in the small intestine in response to feeding and reduce food intake and obesity. Here, we demonstrated that administration of engineered NAPE-expressing E. coli Nissle 1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in mice fed a high-fat diet. Mice that received modified bacteria had dramatically lower food intake, adiposity, insulin resistance, and hepatosteatosis compared with mice receiving standard water or control bacteria. The protective effects conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their removal from the drinking water. Moreover, administration of NAPE-expressing bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight gain. Our results demonstrate that incorporation of appropriately modified bacteria into the gut microbiota has potential as an effective strategy to inhibit the development of metabolic disorders.

Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity

PubMed Central

Chen, Zhongyi; Guo, Lilu; Zhang, Yongqin; L. Walzem, Rosemary; Pendergast, Julie S.; Printz, Richard L.; Morris, Lindsey C.; Matafonova, Elena; Stien, Xavier; Kang, Li; Coulon, Denis; McGuinness, Owen P.; Niswender, Kevin D.; Davies, Sean S.

2014-01-01

Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gut microbiota composition is a contributing factor to the susceptibility of an individual to the development of these disorders; therefore, altering a person’s microbiota may ameliorate disease. One potential microbiome-altering strategy is the incorporation of modified bacteria that express therapeutic factors into the gut microbiota. For example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the N-acylethanolamide (NAE) family of lipids, which are synthesized in the small intestine in response to feeding and reduce food intake and obesity. Here, we demonstrated that administration of engineered NAPE-expressing E. coli Nissle 1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in mice fed a high-fat diet. Mice that received modified bacteria had dramatically lower food intake, adiposity, insulin resistance, and hepatosteatosis compared with mice receiving standard water or control bacteria. The protective effects conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their removal from the drinking water. Moreover, administration of NAPE-expressing bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight gain. Our results demonstrate that incorporation of appropriately modified bacteria into the gut microbiota has potential as an effective strategy to inhibit the development of metabolic disorders. PMID:24960158

A Review of Obesity and Its Relationship with the Built Environment: Implications for Health Educators

ERIC Educational Resources Information Center

Pinzon-Perez, Helda

2007-01-01

Obesity is an important worldwide public health problem. Obesogenic environments have been associated with increasing rates of overweight and obesity. The relationship between obesity and the built environment, along with its implications for health education are discussed in this article.

Juxtapapillary duodenal diverticula early and late clinical and therapeutical implications.

PubMed

Straja, D; Marincaş, M; Alecu, M; Boroghina, G; Simion, L; Stanescu, A; Drilea, E; Brătucu, E

2009-01-01

The aim of this paper is to identify the early and late implications of JPDD for biliary pathology, as well as for endoscopic therapy and classical surgery dealing mainly with lithiasis. This paper is based on a retrospective study comprising a number of 675 ERCP performed on 601 patients between 1997-2007, out of which 399 cases were followed by therapeutic measures. A total of 79 procedures were performed on 65 cases with JPDD. The main criteria were: gender, age, indications regarding the performance of ERCP+/-ES, complications that occurred while carrying out these procedures. In all the cases examined (601) the percentage of JPDD reported was of 10.81%. The rate of complications in the sphincterotomized patients without JPDD was 5.75% and the rate in the sphincterotomized patients with JPDD was 14.89%. In conclusion, the paper discusses the clinical and therapeutic implications of JPDD in biliary pathology. It has been found that JPDD is an important etiological cause for the late diseases occurring after cholelithiasis surgery. JPDD also leads to immediate therapeutic implications such as: difficult cannulation and high incidence of ERCP+/-ES complications.

Health Consequences of Weight Stigma: Implications for Obesity Prevention and Treatment.

PubMed

Puhl, Rebecca; Suh, Young

2015-06-01

Despite decades of research documenting consistent stigma and discrimination against individuals with obesity, weight stigma is rarely considered in obesity prevention and treatment efforts. In recent years, evidence has examined weight stigmatization as a unique contributor to negative health outcomes and behaviors that can promote and exacerbate obesity. This review summarizes findings from published studies within the past 4 years examining the relationship between weight stigma and maladaptive eating behaviors (binge eating and increased food consumption), physical activity, weight status (weight gain and loss and development of obesity), and physiological stress responses. Research evaluating the effects of weight stigma present in obesity-related public health campaigns is also highlighted. Evidence collectively demonstrates negative implications of stigmatization for weight-related health correlates and behaviors and suggests that addressing weight stigma in obesity prevention and treatment is warranted. Key questions for future research to further delineate the health effects of weight stigmatization are summarized.

The Obesity Epidemic: Challenges, Health Initiatives, and Implications for Gastroenterologists

PubMed Central

Hurt, Ryan T.; Kulisek, Christopher; Buchanan, Laura A.

2010-01-01

Obesity is the next major epidemiologic challenge facing today's doctors, with the annual allocation of healthcare resources for the disease and related comorbidities projected to exceed $150 billion in the United States. The incidence of obesity has risen in the United States over the past 30 years; 60% of adults are currently either obese or overweight. Obesity is associated with a higher incidence of a number of diseases, including diabetes, cardiovascular disease, and cancer. Consumption of fast food, trans fatty acids (TFAs), and fructose—combined with increasing portion sizes and decreased physical activity—has been implicated as a potential contributing factor in the obesity crisis. The use of body mass index (BMI) alone is of limited utility for predicting adverse cardiovascular outcomes, but the utility of this measure may be strengthened when combined with waist circumference and other anthropomorphic measurements. Certain public health initiatives have helped to identify and reduce some of the factors contributing to obesity. In New York City and Denmark, for example, such initiatives have succeeded in passing legislation to reduce or remove TFAs from residents' diets. The obesity epidemic will likely change practice for gastroenterologists, as shifts will be seen in the incidence of obesity-related gastrointestinal disorders, disease severity, and the nature of comorbidities. The experience gained with previous epidemiologic problems such as smoking should help involved parties to expand needed health initiatives and increase the likelihood of preventing future generations from suffering the consequences of obesity. PMID:21301632

Sleep duration and overweight/obesity in children: implication for pediatric nursing

PubMed Central

Liu, Jianghong; Zhang, Angelina; Li, Linda

2012-01-01

Purpose The purpose of this study was to review evidence from the last 5 years (2006-2011) regarding a relationship between sleep duration and childhood overweight/obesity. Conclusions Among the 25 studies selected from PubMed and Web of Knowledge databases, all indicated significant associations between short sleep duration and childhood overweight/obesity. Studies explored a range of pediatric populations, methodologies, and potential contributing factors. Practice Implications Childhood sleep duration may be a modifiable risk factor in preventing obesity. In addition to identifying and assessing patients’ sleep habits, nurses play important roles as educators regarding the importance of adequate sleep and promoting it in children. PMID:22734873

Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?

PubMed

Irwin, Nigel; Gault, Victor; Flatt, Peter R

2010-09-01

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone. The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered. Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date. GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.

The JAK/STAT pathway in obesity and diabetes.

PubMed

Gurzov, Esteban N; Stanley, William J; Pappas, Evan G; Thomas, Helen E; Gough, Daniel J

2016-08-01

Diabetes mellitus are complex, multi-organ metabolic pathologies characterized by hyperglycemia. Emerging evidence shows that the highly conserved and potent JAK/STAT signaling pathway is required for normal homeostasis, and, when dysregulated, contributes to the development of obesity and diabetes. In this review, we analyze the role of JAK/STAT activation in the brain, liver, muscle, fat and pancreas, and how this affects the course of the disease. We also consider the therapeutic implications of targeting the JAK/STAT pathway in treatment of obesity and diabetes. © 2016 Federation of European Biochemical Societies.

Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and Clinical Implications.

PubMed

Zhang, Xueli; Liu, Yamin; Shao, Hua; Zheng, Xiao

2017-10-01

The survival rate of lung cancer remains low despite the progress of surgery and chemotherapy. With the increasing comorbidity of obesity in patients with lung cancer, new challenges are emerging in the management of this patient population. A key issue of interest is the prognostic effect of obesity on surgical and chemotherapeutic outcomes in patients with lung cancer, which is fueled by the growing observation of survival benefits in overweight or obese patients. This unexpected inverse relationship between obesity and lung cancer mortality, called the obesity paradox, remains poorly understood. The evolving insights into the heterogeneity of obesity phenotypes and associated biological connections with lung cancer progression in recent years may help explain some of the seemingly paradoxical relationship, and well-designed clinical studies looking at the causal role of obesity-associated molecules are expected. Here, we examine potential biological mechanisms behind the protective effects of obesity in lung cancer. We highlight the need to clarify the clinical implications of this relationship toward an updated intervention strategy in the clinical care of patients with lung cancer and obesity. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases.

PubMed

Richey, Joyce M; Woolcott, Orison

2017-09-14

The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system. Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities. Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).

Dietary capsaicin and its anti-obesity potency: from mechanism to clinical implications

PubMed Central

Zheng, Jia; Zheng, Sheng; Feng, Qianyun; Zhang, Qian

2017-01-01

Obesity is a growing public health problem, which has now been considered as a pandemic non-communicable disease. However, the efficacy of several approaches for weight loss is limited and variable. Thus, alternative anti-obesity treatments are urgently warranted, which should be effective, safe, and widely available. Active compounds isolated from herbs are similar with the practice of Traditional Chinese Medicine, which has a holistic approach that can target to several organs and tissues in the whole body. Capsaicin, a major active compound from chili peppers, has been clearly demonstrated for its numerous beneficial roles in health. In this review, we will focus on the less highlighted aspect, in particular how dietary chili peppers and capsaicin consumption reduce body weight and its potential mechanisms of its anti-obesity effects. With the widespread pandemic of overweight and obesity, the development of more strategies for the treatment of obesity is urgent. Therefore, a better understanding of the role and mechanism of dietary capsaicin consumption and metabolic health can provide critical implications for the early prevention and treatment of obesity. PMID:28424369

Sirtuins-mediators of maternal obesity-induced complications in offspring?

PubMed

Nguyen, Long T; Chen, Hui; Pollock, Carol A; Saad, Sonia

2016-04-01

Obesity is a complex metabolic disease, attributed to diverse and interactive genetic and environmental factors. The associated health consequences of obesity are pleiotropic, with individuals being more susceptible to chronic diseases such as type 2 diabetes mellitus, hypertension, and lipotoxicity-related chronic diseases. The contribution of maternal obesity to the offspring's predisposition to both obesity and its complications is increasingly recognized. Understanding the mechanisms underlying these "transmissible" effects is critical to develop therapeutic interventions to reduce the risk for "programmed" obesity. Sirtuins (SIRTs), particularly SIRT1 and SIRT3, are NAD(+)-dependent deacetylases that regulate metabolic balance and stress responses in both central and peripheral tissues, of which dysregulation is a well-established mediator for the development and effects of obesity. Nevertheless, their implication in the transmissible effects of maternal obesity across generations remains largely elusive. In this review, we examine multiple pathways and systems that are likely to mediate such effects, with particular emphasis on the role of SIRTs.-Nguyen, L. T., Chen, H., Pollock, C. A., Saad, S. Sirtuins-mediators of maternal obesity-induced complications in offspring? © FASEB.

The Childhood Obesity Declines Project: Implications for Research and Evaluation Approaches.

PubMed

Young-Hyman, Deborah; Morris, Kathryn; Kettel Khan, Laura; Dawkins-Lyn, Nicola; Dooyema, Carrie; Harris, Carole; Jernigan, Jan; Ottley, Phyllis; Kauh, Tina

2018-03-01

Childhood obesity remains prevalent and is increasing in some disadvantaged populations. Numerous research, policy and community initiatives are undertaken to impact this pandemic. Understudied are natural experiments. The need to learn from these efforts is paramount. Resulting evidence may not be readily available to inform future research, community initiatives, and policy development/implementation. We discuss the implications of using an adaptation of the Systematic Screening and Assessment (SSA) method to evaluate the Childhood Obesity Declines (COBD) project. The project examined successful initiatives, programs and policies in four diverse communities which were concurrent with significant declines in child obesity. In the context of other research designs and evaluation schemas, rationale for use of SSA is presented. Evidence generated by this method is highlighted and guidance suggested for evaluation of future studies of community-based childhood obesity prevention initiatives. Support for the role of stakeholder collaboratives, in particular the National Collaborative on Childhood Obesity Research, as a synergistic vehicle to accelerate research on childhood obesity is discussed. SSA mapped active processes and provided contextual understanding of multi-level/component simultaneous efforts to reduce rates of childhood obesity in community settings. Initiatives, programs and policies were not necessarily coordinated. And although direct attribution of intervention/initiative/policy components could not be made, the what, by who, how, to whom was temporally associated with statistically significant reductions in childhood obesity. SSA provides evidence for context and processes which are not often evaluated in other data analytic methods. SSA provides an additional tool to layer with other evaluation approaches.

Developing anti-inflammatory therapeutics for patients with osteoarthritis.

PubMed

Philp, Ashleigh M; Davis, Edward T; Jones, Simon W

2017-06-01

OA is the most common joint disorder in the world, but there are no approved therapeutics to prevent disease progression. Historically, OA has been considered a wear-and-tear joint disease, and efforts to identify and develop disease-modifying therapeutics have predominantly focused on direct inhibition of cartilage degeneration. However, there is now increasing evidence that inflammation is a key mediator of OA joint pathology, and also that the link between obesity and OA is not solely due to excessive load-bearing, suggesting therefore that targeting inflammation in OA could be a rewarding therapeutic strategy. In this review we therefore re-evaluate historical clinical trial data on anti-inflammatory therapeutics in OA patients, highlight some of the more promising emerging therapeutic targets and discuss the implications for future clinical trial design. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neurocardiology: Therapeutic Implications for Cardiovascular Disease

PubMed Central

Goldstein, David S.

2016-01-01

SUMMARY The term “neurocardiology” refers to physiologic and pathophysiological interplays of the nervous and cardiovascular systems. This selective review provides an update about cardiovascular therapeutic implications of neurocardiology, with emphasis on disorders involving primary or secondary abnormalities of catecholamine systems. Concepts of scientific integrative medicine help understand these disorders. Scientific integrative medicine is not a treatment method or discipline but a way of thinking that applies systems concepts to acute and chronic disorders of regulation. Some of these concepts include stability by negative feedback regulation, multiple effectors, effector sharing, instability by positive feedback loops, allostasis, and allostatic load. Scientific integrative medicine builds on systems biology but is also distinct in several ways. A large variety of drugs and non-drug treatments are now available or under study for neurocardiologic disorders in which catecholamine systems are hyperfunctional or hypofunctional. The future of therapeutics in neurocardiology is not so much in new curative drugs as in applying scientific integrative medical ideas that take into account concurrent chronic degenerative disorders and interactions of multiple drug and non-drug treatments with each other and with those disorders. PMID:21108771

Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity.

PubMed

Carlucci, Christian; Petrof, Elaine O; Allen-Vercoe, Emma

2016-11-01

The human gut microbiome is a complex ecosystem of fundamental importance to human health. Our increased understanding of gut microbial composition and functional interactions in health and disease states has spurred research efforts examining the gut microbiome as a valuable target for therapeutic intervention. This review provides updated insight into the state of the gut microbiome in recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and obesity while addressing the rationale for the modulation of the gut microbiome using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based therapeutics in pre-clinical or clinical development are discussed. We end by putting this within the context of the current regulatory framework surrounding FMT and related therapies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Stress-induced EGFR trafficking: mechanisms, functions, and therapeutic implications

PubMed Central

Tan, Xiaojun; Lambert, Paul F.; Rapraeger, Alan C.; Anderson, Richard A.

2016-01-01

Epidermal growth factor receptor (EGFR) has fundamental roles in normal physiology and in cancer, making it a rational target for cancer therapy. Surprisingly, however, inhibitors that target canonical, ligand-stimulated EGFR signaling have proven to be largely ineffective in treating many EGFR-dependent cancers. Recent evidence indicates that both intrinsic and therapy-induced cellular stress triggers robust, non-canonical pathways of ligand-independent EGFR trafficking and signaling, which provides cancer cells with a survival advantage and resistance to therapeutics. Here we review the mechanistic regulation of non-canonical EGFR trafficking and signaling, the pathological and therapeutic stresses that activate it, and discuss the implications of this pathway in clinical treatment of EGFR-overexpressing cancers. PMID:26827089

Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

PubMed

Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

2015-01-01

This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic

The Neurobiology of "Food Addiction" and Its Implications for Obesity Treatment and Policy.

PubMed

Carter, Adrian; Hendrikse, Joshua; Lee, Natalia; Yücel, Murat; Verdejo-Garcia, Antonio; Andrews, Zane B.; Hall, Wayne

2016-07-17

There is a growing view that certain foods, particularly those high in refined sugars and fats, are addictive and that some forms of obesity can usefully be treated as a food addiction. This perspective is supported by a growing body of neuroscience research demonstrating that the chronic consumption of energy-dense foods causes changes in the brain's reward pathway that are central to the development and maintenance of drug addiction. Obese and overweight individuals also display patterns of eating behavior that resemble the ways in which addicted individuals consume drugs. We critically review the evidence that some forms of obesity or overeating could be considered a food addiction and argue that the use of food addiction as a diagnostic category is premature. We also examine some of the potential positive and negative clinical, social, and public policy implications of describing obesity as a food addiction that require further investigation.

Individuality and epigenetics in obesity.

PubMed

Campión, J; Milagro, F I; Martínez, J A

2009-07-01

Excessive weight gain arises from the interactions among environmental factors, genetic predisposition and the individual behavior. However, it is becoming evident that interindividual differences in obesity susceptibility depend also on epigenetic factors. Epigenetics studies the heritable changes in gene expression that do not involve changes to the underlying DNA sequence. These processes include DNA methylation, covalent histone modifications, chromatin folding and, more recently described, the regulatory action of miRNAs and polycomb group complexes. In this review, we focus on experimental evidences concerning dietary factors influencing obesity development by epigenetic mechanisms, reporting treatment doses and durations. Moreover, we present a bioinformatic analysis of promoter regions for the search of future epigenetic biomarkers of obesity, including methylation pattern analyses of several obesity-related genes (epiobesigenes), such as FGF2, PTEN, CDKN1A and ESR1, implicated in adipogenesis, SOCS1/SOCS3, in inflammation, and COX7A1 LPL, CAV1, and IGFBP3, in intermediate metabolism and insulin signalling. The identification of those individuals that at an early age could present changes in the methylation profiles of specific genes could help to predict their susceptibility to later develop obesity, which may allow to prevent and follow-up its progress, as well as to research and develop newer therapeutic approaches.

Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity.

PubMed

Derbenev, Andrei V; Zsombok, Andrea

2016-05-01

Diabetes mellitus and obesity, which is a major risk factor in the development of type 2 diabetes mellitus, have reached epidemic proportions worldwide including the USA. The current statistics and forecasts, both short- and long-term, are alarming and predict severe problems in the near future. Therefore, there is a race for developing new compounds, discovering new receptors, or finding alternative solutions to prevent and/or treat the symptoms and complications related to obesity and diabetes mellitus. It is well demonstrated that members of the transient receptor potential (TRP) superfamily play a crucial role in a variety of biological functions both in health and disease. In the recent years, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) were shown to have beneficial effects on whole body metabolism including glucose homeostasis. TRPV1 and TRPA1 have been associated with control of weight, pancreatic function, hormone secretion, thermogenesis, and neuronal function, which suggest a potential therapeutic value of these channels. This review summarizes recent findings regarding TRPV1 and TRPA1 in association with whole body metabolism with emphasis on obese and diabetic conditions.

Medical implications of obesity in horses--lessons for human obesity.

PubMed

Johnson, Philip J; Wiedmeyer, Charles E; Messer, Nat T; Ganjam, Venkataseshu K

2009-01-01

There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. © Diabetes Technology Society

Medical Implications of Obesity in Horses—Lessons for Human Obesity

PubMed Central

Johnson, Philip J.; Wiedmeyer, Charles E.; Messer, Nat T.; Ganjam, Venkataseshu K.

2009-01-01

There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. PMID:20046661

Obesity Weighs down Memory through a Mechanism Involving the Neuroepigenetic Dysregulation of Sirt1

PubMed Central

Heyward, Frankie D.; Gilliam, Daniel; Coleman, Mark A.; Gavin, Cristin F.; Wang, Jing; Kaas, Garrett; Trieu, Richard; Lewis, John; Moulden, Jerome

2016-01-01

Aberrant gene expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment. Whether a dysregulation of epigenetic modifications mediates this disruption in gene transcription has yet to be established. Here we report evidence of obesity-induced alterations in DNA methylation of memory-associated genes, including Sirtuin 1 (Sirt1), within the hippocampus, and thus offer a novel mechanism by which SIRT1 expression within the hippocampus is suppressed during obesity. Forebrain neuron-specific Sirt1 knock-out closely recapitulated the memory deficits exhibited by obese mice, consistent with the hypothesis that the high-fat diet-mediated reduction of hippocampal SIRT1 could be responsible for obesity-linked memory impairment. Obese mice fed a diet supplemented with the SIRT1-activating molecule resveratrol exhibited increased hippocampal SIRT1 activity and preserved hippocampus-dependent memory, further strengthening this conclusion. Thus, our findings suggest that the memory-impairing effects of diet-induced obesity may potentially be mediated by neuroepigenetic dysregulation of SIRT1 within the hippocampus. SIGNIFICANCE STATEMENT Previous studies have implicated transcriptional dysregulation within the hippocampus as being a relevant pathological concomitant of obesity-induced memory impairment, yet a deeper understanding of the basis for, and etiological significance of, transcriptional dysregulation in this context is lacking. Here we present the first evidence of epigenetic dysregulation (i.e., altered DNA methylation and hydroxymethylation) of memory-related genes, including Sirt1, within the hippocampus of obese mice. Furthermore, experiments using transgenic and pharmacological approaches strongly implicate reduced hippocampal SIRT1 as being a principal pathogenic mediator of obesity-induced memory impairment. This paper offers a novel working model that may serve as a conceptual basis for the

Pathologic and Therapeutic Implications for the Cell Biology of Parkin

PubMed Central

Charan, Rakshita A.; LaVoie, Matthew J.

2015-01-01

Mutations in the E3 ligase parkin are the most common cause of autosomal recessive Parkinson's disease (PD), but it is believed that parkin dysfunction may also contribute to idiopathic PD. Since its discovery, parkin has been implicated in supporting multiple neuroprotective pathways, many revolving around the maintenance of mitochondrial health quality control and governance of cell survival. Recent advances across the structure, biochemistry, and cell biology of parkin have provided great insights into the etiology of parkin-linked and idiopathic PD and may ultimately generate novel therapeutic strategies to slow or halt disease progression. This review describes the various pathways in which parkin acts and the mechanisms by which parkin may be targeted for therapeutic intervention. PMID:25697646

Body habitus in heart failure: understanding the mechanisms and clinical significance of the obesity paradox.

PubMed

Parto, Parham; Lavie, Carl J; Arena, Ross; Bond, Samantha; Popovic, Dejana; Ventura, Hector O

2016-11-01

The prevalence of obesity among adults and children worldwide has reached epic proportions and has become a major independent risk factor for the development of heart failure (HF), in addition to a contributor of hypertension and cardiovascular disease. The implications of obesity in the development of HF involve adverse effects on cardiac structure and function. Despite all of this, in the setting of chronic HF, excess body mass is associated with improved clinical outcomes, demonstrating the presence of an obesity paradox. In this review, we will discuss the gender differences, global application, potential mechanisms and role of interventions based on fitness and purposeful weight loss as potential therapeutic strategies.

Neural systems implicated in obesity as an addictive disorder: from biological to behavioral mechanisms.

PubMed

Schulte, Erica M; Yokum, Sonja; Potenza, Marc N; Gearhardt, Ashley N

2016-01-01

Contributing factors to obesity have been identified, yet prevention and treatment efforts have had limited long-term success. It has recently been suggested that some individuals may experience an addictive-like response to certain foods, such as losing control over consumption and continued consumption despite negative consequences. In support, shared biological and behavioral features seem to exist between "food addiction" and traditional substance-use disorders. "Food addiction" may be another important contributor to obesity. The current chapter reviews existing literature regarding neural systems implicated similarly in obesity and addiction, discusses unique considerations for addictive-like eating, and proposes directions for future research regarding "food addiction" as an emerging construct for addiction medicine. © 2016 Elsevier B.V. All rights reserved.

Disrupted chronobiology of sleep and cytoprotection in obesity: possible therapeutic value of melatonin.

PubMed

Cardinali, Daniel P; Pagano, Eleonora S; Scacchi Bernasconi, Pablo A; Reynoso, Roxana; Scacchi, Pablo

2011-01-01

From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states (wakefulness, non-rapid eye movement, NREM, sleep and REM sleep) which are defined by a particular neuroendocrine-immune profile regulating the metabolic balance, body weight and inflammatory responses. Sleep deprivation and circadian disruption in contemporary "24/7 Society" lead to the predominance of pro-orexic and proinflammatory mechanisms that contribute to a pandemic metabolic syndrome (MS) including obesity, diabetes and atherosclerotic disease. Thus, a successful management of MS may require a drug that besides antagonizing the trigger factors of MS could also correct a disturbed sleep-wake rhythm. This review deals with the analysis of the therapeutic validity of melatonin in MS. Melatonin is an effective chronobiotic agent changing the phase and amplitude of the sleep/wake rhythm and having cytoprotective and immunomodulatory properties useful to prevent a number of MS sequels. Several studies support that melatonin can prevent hyperadiposity in animal models of obesity. Melatonin at a low dose (2-5 mg/day) has been used for improving sleep in patients with insomnia and circadian rhythm sleep disorders. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, TK 301). In clinical trials these analogs were employed in doses considerably higher than those usually employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin doses in the range of 50-100 mg/day are needed to assess its therapeutic value in MS.

The New Era of Treatment for Obesity and Metabolic Disorders: Evidence and Expectations for Gut Microbiome Transplantation

PubMed Central

Jayasinghe, Thilini N.; Chiavaroli, Valentina; Holland, David J.; Cutfield, Wayne S.; O'Sullivan, Justin M.

2016-01-01

Key Points The microbiome has been implicated in the development of obesity.Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications.Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an “endocrine” organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity. PMID:26925392

Basic biology and therapeutic implications of lncRNA.

PubMed

Khorkova, O; Hsiao, J; Wahlestedt, C

2015-06-29

Long non-coding RNAs (lncRNA), a class of non-coding RNA molecules recently identified largely due to the efforts of FANTOM, and later GENCODE and ENCODE consortia, have been a subject of intense investigation in the past decade. Extensive efforts to get deeper understanding of lncRNA biology have yielded evidence of their diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation and epigenetic regulation. Here we will briefly review the recent studies in the field of lncRNA biology focusing mostly on mammalian species and discuss their therapeutic implications. Copyright © 2015 Elsevier B.V. All rights reserved.

Progranulin as a biomarker and potential therapeutic agent.

PubMed

Abella, Vanessa; Pino, Jesús; Scotece, Morena; Conde, Javier; Lago, Francisca; Gonzalez-Gay, Miguel Angel; Mera, Antonio; Gómez, Rodolfo; Mobasheri, Ali; Gualillo, Oreste

2017-10-01

Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration. In this review, we summarise the most recent research advances concerning the potential role of progranulin as a therapeutic target and biomarker in cancer, neurodegenerative and inflammatory diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Meta-review of protein network regulating obesity between validated obesity candidate genes in the white adipose tissue of high-fat diet-induced obese C57BL/6J mice.

PubMed

Kim, Eunjung; Kim, Eun Jung; Seo, Seung-Won; Hur, Cheol-Goo; McGregor, Robin A; Choi, Myung-Sook

2014-01-01

Worldwide obesity and related comorbidities are increasing, but identifying new therapeutic targets remains a challenge. A plethora of microarray studies in diet-induced obesity models has provided large datasets of obesity associated genes. In this review, we describe an approach to examine the underlying molecular network regulating obesity, and we discuss interactions between obesity candidate genes. We conducted network analysis on functional protein-protein interactions associated with 25 obesity candidate genes identified in a literature-driven approach based on published microarray studies of diet-induced obesity. The obesity candidate genes were closely associated with lipid metabolism and inflammation. Peroxisome proliferator activated receptor gamma (Pparg) appeared to be a core obesity gene, and obesity candidate genes were highly interconnected, suggesting a coordinately regulated molecular network in adipose tissue. In conclusion, the current network analysis approach may help elucidate the underlying molecular network regulating obesity and identify anti-obesity targets for therapeutic intervention.

Host manipulation by cancer cells: Expectations, facts, and therapeutic implications.

PubMed

Tissot, Tazzio; Arnal, Audrey; Jacqueline, Camille; Poulin, Robert; Lefèvre, Thierry; Mery, Frédéric; Renaud, François; Roche, Benjamin; Massol, François; Salzet, Michel; Ewald, Paul; Tasiemski, Aurélie; Ujvari, Beata; Thomas, Frédéric

2016-03-01

Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. © 2016 WILEY Periodicals, Inc.

A scoping review of epidemiologic risk factors for pediatric obesity: Implications for future childhood obesity and dental caries prevention research.

PubMed

Chi, Donald L; Luu, Monique; Chu, Frances

2017-06-01

important implications for future oral health research aimed at preventing childhood obesity and dental caries. Epidemiologic knowledge gleaned from the literature can be used to develop rigorous interventions and programs aimed at preventing these highly prevalent diseases and improving health outcomes for children. © 2017 American Association of Public Health Dentistry.

Interactome of Obesity: Obesidome : Genetic Obesity, Stress Induced Obesity, Pathogenic Obesity Interaction.

PubMed

Geronikolou, Styliani A; Pavlopoulou, Athanasia; Cokkinos, Dennis; Chrousos, George

2017-01-01

Obesity is a chronic disease of increasing prevalence reaching epidemic proportions. Genetic defects as well as epigenetic effects contribute to the obesity phenotype. Investigating gene (e.g. MC4R defects)-environment (behavior, infectious agents, stress) interactions is a relative new field of great research interest. In this study, we have made an effort to create an interactome (henceforth referred to as "obesidome"), where extrinsic stressors response, intrinsic predisposition, immunity response to inflammation and autonomous nervous system implications are integrated. These pathways are presented in one interactome network for the first time. In our study, obesity-related genes/gene products were found to form a complex interactions network.

Visceral obesity and psychosocial stress: a generalised control theory model

NASA Astrophysics Data System (ADS)

Wallace, Rodrick

2016-07-01

The linking of control theory and information theory via the Data Rate Theorem and its generalisations allows for construction of necessary conditions statistical models of body mass regulation in the context of interaction with a complex dynamic environment. By focusing on the stress-related induction of central obesity via failure of HPA axis regulation, we explore implications for strategies of prevention and treatment. It rapidly becomes evident that individual-centred biomedical reductionism is an inadequate paradigm. Without mitigation of HPA axis or related dysfunctions arising from social pathologies of power imbalance, economic insecurity, and so on, it is unlikely that permanent changes in visceral obesity for individuals can be maintained without constant therapeutic effort, an expensive - and likely unsustainable - public policy.

Integrins in bone metastasis formation and potential therapeutic implications.

PubMed

Clëzardin, P

2009-11-01

Integrins constitute a family of cell surface receptors that are heterodimers composed of noncovalently associated alpha and beta subunits. Integrins bind to extracellular matrix proteins and immunogobulin superfamily molecules. They exert a stringent control on cell migration, survival and proliferation. However, their expression and functions are often deregulated in cancer, and many lines of evidence implicate them as key regulators during progression from primary tumor growth to metastasis. Here, we review the role of integrins in bone metastasis formation and present evidence that the use of integrin-targeted therapeutic agents may be an efficient strategy to block tumor metastasis.

The Sequencing of a College Degree during the Transition to Adulthood: Implications for Obesity*

PubMed Central

Miech, Richard Allen; Shanahan, Michael J.; Boardman, Jason; Bauldry, Shawn

2016-01-01

In this study we consider the health implications of the sequencing of a college degree vis-à-vis familial roles during the transition to adulthood. We hypothesize that people who earned a college degree before assuming familial roles will have better health than people who earned a college degree afterwards. To test this hypothesis, we focus on obesity and use data from the National Longitudinal Study of Adolescent Health. Results show that marriage before completion of college was associated with a 50% higher probability of becoming obese when compared with marriage after completion of college. Parenthood before college completion was associated with a greater-than two-fold increase in the probability of becoming obese when compared to parenthood afterwards for Black men. These findings suggest that the well-established association of education with health depends on its place in a sequence of roles. PMID:26022787

Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets

PubMed Central

Vasconcelos, Luiz H. C.; Souza, Iara L. L.; Pinheiro, Lílian S.; Silva, Bagnólia A.

2016-01-01

Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus, and Web of Science) to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance, and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation. PMID:27065858

[Histological and molecular classification of endometrial carcinoma and therapeutical implications].

PubMed

Genestie, Catherine; Leary, Alexandra; Devouassoux, Mojgan; Auguste, Aurélie

2017-12-01

Endometrial cancer is the fourth cause of cancer in women in France and is the second most common cancer of the gynecologic cancer after breast cancer with 7275 new cases in 2012. The incidence of this neoplasm tends to increase with population aging, diabetes and obesity's augmentation. In rare cases, a hereditary factor has been described: Lynch's syndrome. The therapeutic management of the patient depends on the endometrial biopsy which specifies the histological type and the histo-prognostic grade as well as the MRI which allow the tumor staging. Within the last decade, improvement in technologies such as genomic, transcriptomic and histological analyses, allowed the establishment of new and finer classifications of endometrial carcinomas. The latest classification proposed by The Cancer Genomic Atlas (TCGA), has been made routinely applicable through the international consortium TransPORTEC. It consists of 4 groups listed from good to poor prognosis: (1) ultra-mutated "POLE"; (2) hyper-mutated "MSI"; (3) low copy number "NSMP" and (4) high number of copies "TP53 mutated" (serous-like). This integrated characterization combined with mutational data opens new opportunities for therapeutic strategies. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

PubMed Central

Kim, Byeong Mo; Hong, Yunkyung; Lee, Seunghoon; Liu, Pengda; Lim, Ji Hong; Lee, Yong Heon; Lee, Tae Ho; Chang, Kyu Tae; Hong, Yonggeun

2015-01-01

Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR. PMID:26569225

Hedgehog Signaling in Prostate Cancer and Its Therapeutic Implication

PubMed Central

Gonnissen, Annelies; Isebaert, Sofie; Haustermans, Karin

2013-01-01

Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition. PMID:23880852

Popular edible seaweed, Gelidium amansii prevents against diet-induced obesity.

PubMed

Kang, Min-Cheol; Kang, Nalae; Kim, Seo-Young; Lima, Inês S; Ko, Seok-Chun; Kim, Young-Tae; Kim, Young-Bum; Jeung, Hee-Do; Choi, Kwang-Sik; Jeon, You-Jin

2016-04-01

The popular edible seaweed, Gelidium amansii is broadly used as food worldwide. To determine whether G. amansii extract (GAE) has protective effects on obesity, mice fed a high-fat diet (HFD) treated with GAE (1 and 3 %) were studied. After 12 weeks of GAE treatment, body weight was greatly decreased in mice fed a high-fat diet. This effect could be due to decreased adipogenesis, as evidenced by the fact that GAE suppressed adipogenic gene expression in adipocytes. In addition, blood glucose and serum insulin levels were reduced by GAE treatment in mice fed a high-fat diet, suggesting improvement in glucose metabolism. GAE supplementation also led to a significant decrease in total cholesterol and triglyceride levels. These data are further confirmed by H&E staining. Our findings indicate that Gelidium amansii prevents against the development of diet-induced obesity, and further implicate that GAE supplementation could be the therapeutical option for treatment of metabolic disorder such as obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity.

PubMed

Ferguson, Scott W; Nguyen, Juliane

2016-04-28

Harnessing exosomes as therapeutic drug delivery vehicles requires a better understanding of exosomal composition and their mode of action. A full appreciation of all the exosomal components (proteins, lipids, and RNA content) will be important for the design of effective exosome-based or exosome-mimicking drug carriers. In this review we describe the presence of rarely studied, non-coding RNAs that exist in high numbers in exosomes. We discuss the implications of the molecular composition and heterogeneity of exosomes on their biological and therapeutic effects. Finally, we highlight outstanding questions with regard to RNA loading into exosomes, analytical methods to sort exosomes and their sub-populations, and the effects of exosomal proteins and lipids on recipient cells. Investigations into these facets of exosome biology will further advance the field, could lead to the clinical translation of exosome-based therapeutics, and aid in the reverse-engineering of synthetic exosomes. Although synthetic exosomes are still an underexplored area, they could offer researchers a way to manufacture exosomes with highly defined structure, composition, and function. Copyright © 2016 Elsevier B.V. All rights reserved.

Albumin in chronic liver disease: structure, functions and therapeutic implications.

PubMed

Spinella, Rosaria; Sawhney, Rohit; Jalan, Rajiv

2016-01-01

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.

Childhood obesity case statement.

PubMed

Esposito, Paul W; Caskey, Paul; Heaton, Lisa E; Otsuka, Norman

2013-04-01

The goal of this publication is to raise awareness of the impact of childhood obesity on the musculoskeletal health of children and its potential long-term implications. Relevant articles dealing with musculoskeletal disorders either caused by or worsened by childhood obesity were reviewed through a Pub Med search. Efforts to recognize and combat the childhood obesity epidemic were also identified through Internet search engines. This case statement was then reviewed by the members of the pediatric specialty group of the US Bone and Joint Initiative, which represents an extensive number of organizations dealing with musculoskeletal health. Multiple musculoskeletal disorders are clearly caused by or worsened by childhood obesity. The review of the literature clearly demonstrates the increased frequency and severity of many childhood musculoskeletal disorders. Concerns about the long-term implications of these childhood onset disorders such as pain and degenerative changes into adulthood are clearly recognized by all the member organizations of the US Bone and Joint Initiative. It is imperative to recognize the long-term implications of musculoskeletal disorders caused by or worsened by childhood obesity. It is also important to recognize that the ability to exercise comfortably is a key factor to developing a healthy lifestyle and maintaining a healthy body weight. Efforts to develop reasonable and acceptable programs to increase physical activity by all facets of society should be supported. Further research into the long-term implications of childhood musculoskeletal disorders related to childhood obesity is necessary. Copyright © 2013 Elsevier Inc. All rights reserved.

Obesity pharmacotherapy: What is next?

PubMed Central

Colon-Gonzalez, Francheska; Kim, Gilbert W.; Lin, Jieru E.; Valentino, Michael A.; Waldman, Scott A.

2014-01-01

The increase in obesity in the Unites States and around the world in the last decade is overwhelming. The number of overweight adults in the world surpassed 1 billion in 2008. Health hazards associated with obesity are serious and include heart disease, sleep apnea, diabetes, and cancer. Although lifestyle modifications are the most straightforward way to control weight, a large portion of the population may not be able to rely on this modality alone. Thus, the development of anti-obesity therapeutics represents a major unmet medical need. Historically, anti-obesity pharmacotherapies have been unsafe and minimally efficacious. A better understanding of the biology of appetite and metabolism provides an opportunity to develop drugs that may offer safer and more effective alternatives for weight management. This review discusses drugs that are currently on the market and in development as anti-obesity therapeutics based on their target and mechanism of action. It should serve as a roadmap to establish expectations for the near future for anti-obesity drug development. PMID:23103610

Identification of HNF1A-MODY and HNF4A-MODY in Irish families: phenotypic characteristics and therapeutic implications.

PubMed

Kyithar, M P; Bacon, S; Pannu, K K; Rizvi, S R; Colclough, K; Ellard, S; Byrne, M M

2011-12-01

The prevalence of hepatocyte nuclear factor (HNF)-1A and HNF4A mutations, and the clinical implications following the genetic diagnosis of maturity-onset diabetes of the young (MODY) in the Irish population, remain unknown. The aim of this study was to establish the occurrence of HNF1A and HNF4A mutations in subjects classified clinically as MODY to identify novel mutations, and to determine the phenotypic features and response to therapy. A total of 36 unrelated index cases with a clinical diagnosis of MODY were analyzed for HNF1A/HNF4A mutations. OGTT was performed to determine the degree of glucose tolerance and insulin secretory response. Also, 38 relatives underwent OGTT and were tested for the relevant known mutations. HNF1A-/HNF4A-MODY subjects were compared with nine HNF1A mutation-negative relatives and 20 type 2 diabetic (T2DM) patients. Seven different HNF1A mutations were identified in 11/36 (30.5%) index cases, two of which were novel (S352fsdelG and F426X), as well as two novel HNF4A mutations (M1? and R290C; 6%). Family screening revealed 20 subjects with HNF1A and seven with HNF4A mutations. Only 51.6% of HNF1A mutation carriers were diagnosed with diabetes by age 25 years; 11 of the mutation carriers were overweight and four were obese. Insulin secretory response to glucose was significantly lower in HNF1A-MODY subjects than in T2DM patients and HNF1A mutation-negative relatives (P=0.01). Therapeutic changes occurred in 48% of mutation carriers following genetic diagnosis. There was an HNF1A-MODY pick-up rate of 30.5% and an HNF4A-MODY pick-up rate of 6% in Irish MODY families. Genetically confirmed MODY has significant therapeutic implications. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Clinical, molecular genetics and therapeutic aspects of syndromic obesity.

PubMed

Geets, E; Meuwissen, M E C; Van Hul, W

2018-04-26

Obesity has become a major health problem worldwide. To date, more than 25 different syndromic forms of obesity are known in which one (monogenic) or multiple (polygenic) genes are involved. This review gives an overview of these forms and focuses more in detail on six syndromes: Prader Willi Syndrome and Prader Willi like phenotype, Bardet Biedl Syndrome, Alström Syndrome, Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation syndrome and 16p11.2 (micro)deletions. Years of research provided plenty of information on the molecular genetics of these disorders and the obesity phenotype leading to a more individualized treatment of the symptoms, however, a lot of questions still remain unanswered. As these obesity syndromes have different signs and symptoms in common, it makes it difficult to accurately diagnose patients which may result in inappropriate treatment of the disease. Therefore, the big challenge for clinicians and scientists is to more clearly differentiate all syndromic forms of obesity to provide conclusive genetic explanations and eventually deliver accurate genetic counseling and treatment. In addition, further delineation of the (functions of the) underlying genes with the use of array- or next generation sequencing-based technology will be helpful to unravel the mechanisms of energy metabolism in the general population. This article is protected by copyright. All rights reserved.

Therapeutic implication of HER2 in advanced biliary tract cancer

PubMed Central

Cha, Yongjun; Ha, Hyerim; Park, Ji Eun; Bang, Ju-Hee; Jin, Mei Hua; Lee, Kyung-Hun; Kim, Tae-Yong; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Oh, Do-Youn; Bang, Yung-Jue

2016-01-01

Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. PMID:27517322

Integrating Fundamental Concepts of Obesity and Eating Disorders: Implications for the Obesity Epidemic

PubMed Central

2015-01-01

Physiological mechanisms promote weight gain after famine. Because eating disorders, obesity, and dieting limit food intake, they are famine-like experiences. The development of the concept of meeting an ideal weight was the beginning of increasing obesity. Weight stigma, the perception of being fat, lack of understanding of normal growth and development, and increased concern about obesity on the part of health providers, parents, and caregivers have reinforced each other to promote dieting. Because weight suppression and disinhibition provoke long-term weight increase, dieting is a major factor producing the obesity epidemic. The integrated eating disorder–obesity theory included in this article emphasizes that, contrary to dieters, lifetime weight maintainers depend on physiological processes to control weight and experience minimal weight change. PMID:25713933

Effects of Olive Oil on TNF-α and IL-6 in Humans: Implication in Obesity and Frailty.

PubMed

Yarla, Nagendra S; Polito, Angela; Peluso, Ilaria

2018-01-01

Tumor necrosis factor-alpha (TNF)-α and interleukin (IL)-6 are important mediators of chronic low-grade systemic inflammation. The latter plays a central role in several obesity-related pathologies, such as diabetes, metabolic syndrome and cardiovascular diseases. Besides, these cytokines have been also implicated in geriatric and cancer-induced anorexia, cachexia, sarcopenia and frailty. Potential interventions for both obesity and frailty include dietary advice and nutraceuticals. In this context, the consumption of olive oil (OO) has been associated with the health effects of the Mediterranean diet (Med-diet). This review is aimed to discuss the OO-mediated modulation of TNF- α and IL-6 in human studies and the potential implication in obesity and frailty. The reviewed studies suggest that the improvement of postprandial TNF-α and IL-6 observed with OO consumption is affected by body mass index (BMI). The effects on TNF-α and IL-6 after medium and long-term consumptions involved many factors and the cross-talk between adipose tissue, liver, skeletal muscle and brain. Major anti-inflammatory effects were observed when OO was consumed with Med-diet, which is associated with healthy behaviors. In this context, the role of microbioma- polyphenols, diet-gene and exercise-gene interactions in the effects of OO on immune-mediated inflammatory responses involved in obesity and frailty deserves further investigation. Further studies are needed to clarify the effect of OO net of possible synergistic effects with other dietary and lifestyle factors of Mediterranean area. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Epigenetic regulation in obesity.

PubMed

Drummond, Elaine M; Gibney, Eileen R

2013-07-01

Research suggests that 65% of variation in obesity is genetic. However, much of the known genetic associations have little known function and their effect size small, thus the gene-environment interaction, including epigenetic influences on gene expression, is suggested to be an important factor in the susceptibilty to obesity. This review will explore the potential of epigenetic markers to influence expression of genes associated with obesity. Epigenetic changes in utero are known to have direct implications on the phenotype of the offspring. More recently work has focused on how such epigenetic changes continue to regulate risk of obesity from infancy through to adulthood. Work has shown that, for example, hypomethylation of the MC4 gene causes an increase in expression, and has a direct impact on appetite and intake, and thus influences risk of obesity. Similar influences are also seen in other aspects of obesity including inflammation and adiposity. Maternal diet during foetal development has many epigenetic implications, which affect the offspring's risk factors for obesity during childhood and adulthood, and even in subsequent generations. Genes associated with risk of obesity, are susceptible to epigenetic mutations, which have subsequent effects on disease mechanisms, such as appetite and impaired glucose and insulin tolerance.

Obesity and PCOS: Implications for Diagnosis and Treatment

PubMed Central

Legro, Richard S.

2013-01-01

There appears to be an epidemic of both obesity and polycystic ovary syndrome (PCOS) in the world today. However, obesity per se is not a part of the phenotype in many parts of the world. Obesity is likely not a cause of PCOS, as the high prevalence of PCOS among relatively thin populations demonstrates. However, obesity does exacerbate many aspects of the phenotype, especially cardiovascular risk factors such as glucose intolerance and dyslipidemia. It is also associated with a poor response to infertility treatment and likely an increased risk for pregnancy complications in those women who do conceive. Although most treatments of obesity, with the exception of bariatric surgery, achieve modest reductions in weight and improvements in the PCOS phenotype, encouraging weight loss in the obese patient remains one of the front-line therapies. However, further studies are needed to identify the best treatments, and the role of lifestyle therapies in women of normal weight with PCOS is uncertain. PMID:23074008

The Critical Care Obesity Paradox and Implications for Nutrition Support.

PubMed

Patel, Jayshil J; Rosenthal, Martin D; Miller, Keith R; Codner, Panna; Kiraly, Laszlo; Martindale, Robert G

2016-09-01

Obesity is a leading cause of preventable death worldwide. The prevalence of obesity has been increasing and is associated with an increased risk for other co-morbidities. In the critical care setting, nearly one third of patients are obese. Obese critically ill patients pose significant physical and on-physical challenges to providers, including optimization of nutrition therapy. Intuitively, obese patients would have worse critical care-related outcome. On the contrary, emerging data suggests that critically ill obese patients have improved outcomes, and this phenomenon has been coined "the obesity paradox." The purposes of this review will be to outline the historical views and pathophysiology of obesity and epidemiology of obesity, describe the challenges associated with obesity in the intensive care unit setting, review critical care outcomes in the obese, define the obesity-critical care paradox, and identify the challenges and role of nutrition support in the critically ill obese patient.

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

PubMed Central

2015-01-01

Abstract Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686–729. PMID:25546574

Obesity and PCOS: implications for diagnosis and treatment.

PubMed

Legro, Richard S

2012-12-01

There appears to be an epidemic of both obesity and polycystic ovary syndrome (PCOS) in the world today. However, obesity per se is not a part of the phenotype in many parts of the world. Obesity is likely not a cause of PCOS, as the high prevalence of PCOS among relatively thin populations demonstrates. However, obesity does exacerbate many aspects of the phenotype, especially cardiovascular risk factors such as glucose intolerance and dyslipidemia. It is also associated with a poor response to infertility treatment and likely an increased risk for pregnancy complications in those women who do conceive. Although most treatments of obesity, with the exception of bariatric surgery, achieve modest reductions in weight and improvements in the PCOS phenotype, encouraging weight loss in the obese patient remains one of the front-line therapies. However, further studies are needed to identify the best treatments, and the role of lifestyle therapies in women of normal weight with PCOS is uncertain. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Biomechanical Implications of Obesity in K-12 Learners

ERIC Educational Resources Information Center

Strohmeyer, Scott

2007-01-01

Few biomechanical studies have examined obese individuals as primary subjects. However, some mechanical differences have been identified between overweight or obese individuals and nonoverweight movers. It is not clear how obesity affects the onset of osteoarthritis, for example, but it is evident that obesity does place significant limitations on…

New ADCY3 Variants Dance in Obesity Etiology.

PubMed

Tian, Yan; Peng, Boqiang; Fu, Xianghui

2018-02-14

The genetic etiology for obesity-related traits remains elusive. Recent studies link novel ADCY3 variants to obesity and diabetes, and identify an important role of ADCY3-mediated signaling at neuronal primary cilia in the predisposition of obesity. These findings provide new information on obesity etiology and suggest potential anti-obesity therapeutic strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

The key role of psychosocial risk on therapeutic outcome in obese children and adolescents. Results from a longitudinal multicenter study.

PubMed

Röbl, Markus; de Souza, Martin; Schiel, Ralf; Gellhaus, Ines; Zwiauer, Karl; Holl, Reinhard W; Wiegand, Susanna

2013-01-01

Childhood obesity is high on the global public health agenda. Although risk factors are well known, the influence of social risk on the therapeutic outcome of lifestyle intervention is poorly examined. This study aims to investigate the influence of migration background, low education, and parental unemployment. 62,147 patients participated in multidimensional lifestyle intervention programs in 179 pediatric obesity centers. Data were collected using standardized software for longitudinal multicenter documentation. 12,305 (19.8%) attended care for 6-24 months, undergoing an intensive therapy period and subsequent follow-ups for up to 3 years. A cumulative social risk score was calculated based on different risk indicators. Migration background, low education, and parental employment significantly influenced the outcome of lifestyle intervention. The observed BMI-SDS reduction was significantly higher in the subgroup with low social risks factors (Δ BMI-SDS -0.19) compared to those presenting moderate (Δ BMI-SDS -0.14) and high social risk (Δ BMI-SDS -0.11). Our data underline the effect of children's social setting on the outcome of multidimensional lifestyle intervention. The presence of a high social risk burden is a negative predictor for successful weight loss. Specific therapeutic programs need to be developed for disadvantaged children and adolescents. Copyright © 2013 S. Karger GmbH, Freiburg

Obesity, Metabolic Syndrome, and Dietary Therapeutical Approaches with a Special Focus on Nutraceuticals (Polyphenols): A Mini-Review.

PubMed

Ríos-Hoyo, Alejandro; Cortés, María José; Ríos-Ontiveros, Huguette; Meaney, Eduardo; Ceballos, Guillermo; Gutiérrez-Salmeán, Gabriela

2014-01-01

More than half of all global deaths in 2010 were related to non-communicable diseases, including obesity, cancers, diabetes, and cardiovascular illnesses. It has been suggested that the alarming increase in the incidence of cardiovascular disease is the epidemiologic result of a nutrition transition characterized by dietary patterns featuring an increase in the intake of total fat, cholesterol, sugars, and other refined carbohydrates, concomitant with low consumption of polyunsaturated fatty acids and fiber. Although traditional dietary approaches have proven successful as part of the treatment for obesity and cardiometabolic derangements within clinical trial scenarios, they lack effectiveness in the long term, mainly due to poor compliance. Research has thus turned its attention to nutraceutics, nutrients that have the ability to modulate physiological and pathophysiological molecular mechanisms, thus resulting in favorable health outcomes. Polyphenols have been considered as among the bioactive molecules as they are thought to yield beneficial effects by exerting antioxidant activity; however, there are other--and even more robust--metabolic pathways through which polyphenols enhance cardiovascular health, such as via promoting vasodilatory, anti-atherogenic, antithrombotic, and anti-inflammatory effects. No standard dose has yet been determined, as the effects greatly vary among polyphenols and food sources; thus, there is an imperative need to generate more evidence in order to support dietary recommendations aimed at the prevention and therapeutics of obesity and its associated cardiometabolic diseases.

BET inhibitors in metastatic prostate cancer: therapeutic implications and rational drug combinations.

PubMed

Markowski, Mark C; De Marzo, Angelo M; Antonarakis, Emmanuel S

2017-12-01

The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas covered: We speculate that a combination approach using inhibitors of BET proteins (BETi) with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer. Preclinical data has identified several molecular targets that may enhance the effect of BET inhibition in the clinic. This review will summarize the known preclinical data implicating BET as an important therapeutic target in advanced prostate cancer, highlight the ongoing clinical trials targeting this protein family, and speculate on rationale combination strategies using BETi together with other agents in prostate cancer. A literature search using Pubmed was performed for this review. Expert opinion: Use of BETi in the treatment of mCRPC patients may require the addition of a second novel agent.

DGAT inhibitors for obesity.

PubMed

Matsuda, Daisuke; Tomoda, Hiroshi

2007-10-01

Obesity is characterized by the accumulation of triacylglycerol in adipocytes. Diacylglycerol acyltransferase (DGAT) catalyzes the final reaction of triacylgycerol synthesis. Two isozymes of DGAT, DGAT1 and DGAT2, have been reported. Increased DGAT2 activity has a role in steatosis, while DGAT1 plays a role in very (V)LDL synthesis; increased plasma VLDL concentrations may promote obesity and thus DGAT1 is considered a potential therapeutic target of inhibition for obesity control. Several DGAT inhibitors of natural and synthetic origin have been reported, and their future prospect as anti-obesity drugs is discussed in this review.

Physiological and management implications of obesity in critical illness.

PubMed

Shashaty, Michael G S; Stapleton, Renee D

2014-10-01

Obesity is highly prevalent in the United States and is becoming increasingly common worldwide. The anatomic and physiological changes that occur in obese individuals may have an impact across the spectrum of critical illness. Obese patients may be more susceptible to hypoxemia and hypercapnia. During mechanical ventilation, elevated end-expiratory pressures may be required to improve lung compliance and to prevent ventilation-perfusion mismatch due to distal airway collapse. Several studies have shown an increased risk of organ dysfunction such as the acute respiratory distress syndrome and acute kidney injury in obese patients. Predisposition to ventricular hypertrophy and increases in blood volume should be considered in fluid management decisions. Obese patients have accelerated muscle losses in critical illness, making nutrition essential, although the optimal predictive equation to estimate nutritional needs or formulation for obese patients is not well established. Many common intensive care unit medications are not well studied in obese patients, necessitating understanding of pharmacokinetic concepts and consultation with pharmacists. Obesity is associated with higher risk of deep venous thrombosis and catheter-associated bloodstream infections, likely related to greater average catheter dwell times. Logistical issues such as blood pressure cuff sizing, ultrasound assistance for procedures, diminished quality of some imaging modalities, and capabilities of hospital equipment such as beds and lifts are important considerations. Despite the physiological alterations and logistical challenges involved, it is not clear whether obesity has an effect on mortality or long-term outcomes from critical illness. Effects may vary by type of critical illness, obesity severity, and obesity-associated comorbidities.

Dermatomyositis and myastenia gravis: An uncommon association with therapeutic implications.

PubMed

Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Méndez Perles, Clara; Barbadillo, Carmen; Godoy, Hildegarda; Andréu, José Luis

2015-01-01

The association of dermatomyositis with myasthenia gravis (MG) is uncommon, having been reported so far in only 26 cases. We report the case of a 69 year-old man diagnosed with MG two years ago and currently treated with piridostigmyne. The patient developed acute proximal weakness, shoulder pain and elevated creatine-kinase (CK). He also developed generalized facial erythema and Gottron's papules. Laboratory tests showed positive antinuclear and anti-Mi2 antibodies. Further analysis confirmed CK levels above 1000 U/l. The clinical management of the patient and the therapeutic implications derived from the coexistence of both entities are discusssed. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Metabolically Healthy Obesity: Personalised and Public Health Implications.

PubMed

Phillips, Catherine M

2016-04-01

Obesity is a heterogeneous condition; thus, metabolic abnormalities and cardiometabolic risk vary among obese individuals, with a significant proportion considered to be metabolically healthy. However, whether these individuals are truly healthy remains controversial and, therefore, a better understanding of such phenotypes may offer opportunities to improve current obesity diagnosis, intervention, and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Obesity: Pathophysiology and Intervention

PubMed Central

Zhang, Yi; Liu, Ju; Yao, Jianliang; Ji, Gang; Qian, Long; Wang, Jing; Zhang, Guansheng; Tian, Jie; Nie, Yongzhan; Zhang, Yi Edi.; Gold, Mark S.; Liu, Yijun

2014-01-01

Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity. PMID:25412152

Dynamic model predicting overweight, obesity, and extreme obesity prevalence trends.

PubMed

Thomas, Diana M; Weedermann, Marion; Fuemmeler, Bernard F; Martin, Corby K; Dhurandhar, Nikhil V; Bredlau, Carl; Heymsfield, Steven B; Ravussin, Eric; Bouchard, Claude

2014-02-01

Obesity prevalence in the United States appears to be leveling, but the reasons behind the plateau remain unknown. Mechanistic insights can be provided from a mathematical model. The objective of this study is to model known multiple population parameters associated with changes in body mass index (BMI) classes and to establish conditions under which obesity prevalence will plateau. A differential equation system was developed that predicts population-wide obesity prevalence trends. The model considers both social and nonsocial influences on weight gain, incorporates other known parameters affecting obesity trends, and allows for country specific population growth. The dynamic model predicts that: obesity prevalence is a function of birthrate and the probability of being born in an obesogenic environment; obesity prevalence will plateau independent of current prevention strategies; and the US prevalence of overweight, obesity, and extreme obesity will plateau by about 2030 at 28%, 32%, and 9% respectively. The US prevalence of obesity is stabilizing and will plateau, independent of current preventative strategies. This trend has important implications in accurately evaluating the impact of various anti-obesity strategies aimed at reducing obesity prevalence. Copyright © 2013 The Obesity Society.

Assessment of Vitamin D Status and Response to Vitamin D3 in Obese and Non-Obese Iranian Children.

PubMed

Motlaghzadeh, Yasaman; Sayarifard, Fatemeh; Allahverdi, Bahar; Rabbani, Ali; Setoodeh, Aria; Sayarifard, Azadeh; Abbasi, Farzaneh; Haghi-Ashtiani, Mohammad-Taghi; Rahimi-Froushani, Abbas

2016-08-01

Obesity seems to be a critical issue nowadays because of its high prevalence and its adverse effects on health. There is some evidence indicating the relationship between obesity and lower serum 25-hydroxyvitamin D [25(OH)D] concentration. The aim of the present study was to examine serum 25(OH)D status of obese and non-obese Iranian children and compare their therapeutic response with identical oral vitamin D3 treatment. In a non-randomized clinical trial, serum 25(OH)D level of 45 obese and 45 non-obese Iranian children aged 2-14 years was measured. Those with serum 25(OH)D status <30 ng/ml (73 cases) were treated with one pearl of vitamin D3 (50 000 International Units) once a week for 6 weeks. Serum vitamin D was measured once more 2 weeks after treatment. The frequency of hypovitaminosis D was 43/45 (95.6%) in obese and 30/45 (66.7%) in non-obese children at baseline (p < 0.001). After treatment of 73 cases (43 obese, 30 non-obese), the above percentages were decreased to 24/43 (55.8%) and 1/30 (3.3%), respectively (p < 0.001). Our study demonstrated a high frequency of vitamin D deficiency among Iranian children, particularly the obese ones. Moreover, low therapeutic response in the obese group is witnessed. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuroendocrine circuits governing energy balance and stress regulation: functional overlap and therapeutic implications

PubMed Central

Ulrich-Lai, Yvonne M.; Ryan, Karen K.

2014-01-01

Significant co-morbidities between obesity-related metabolic disease and stress-related psychological disorders suggest important functional interactions between energy balance and brain stress integration. Largely overlapping neural circuits control these systems, and this anatomical arrangement optimizes opportunities for mutual influence. Here we first review the current literature identifying effects of metabolic neuroendocrine signals on stress regulation, and vice versa. Next, the contributions of reward driven food intake to these metabolic and stress interactions are discussed. Lastly, we consider the inter-relationships among metabolism, stress and reward in light of their important implications in the development of therapies for metabolism- or stress-related disease. PMID:24630812

Influence of maternal obesity on the long-term health of offspring

PubMed Central

Godfrey, Keith M.; Reynolds, Rebecca M.; Prescott, Susan L.; Nyirenda, Moffat; Jaddoe, Vincent W.V.; Eriksson, Johan G.; Broekman, Birit F.P

2017-01-01

Alongside its immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of health in the offspring during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on the offspring’s risks of obesity, coronary heart disease, stroke, type 2 diabetes and asthma. Maternal obesity may also lead to poorer cognitive performance in the offspring and an increased risk of neurodevelopmental disorders including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious disease related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, mediated at least in part through changes in epigenetic processes including alternations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight prior to pregnancy have a reduced risk of obesity, to date few controlled intervention studies have reversed maternal obesity and examined the consequences for the offspring. The long term effects of maternal obesity may have profound public health implications and indicate the urgency of studies on causality, underlying mechanisms and effective interventions to reverse the epidemic of obesity in women of child-bearing age and to mitigate its consequences for the offspring. PMID:27743978

Modeling the clinical and economic implications of obesity using microsimulation.

PubMed

Su, W; Huang, J; Chen, F; Iacobucci, W; Mocarski, M; Dall, T M; Perreault, L

2015-01-01

The obesity epidemic has raised considerable public health concerns, but there are few validated longitudinal simulation models examining the human and economic cost of obesity. This paper describes a microsimulation model as a comprehensive tool to understand the relationship between body weight, health, and economic outcomes. Patient health and economic outcomes were simulated annually over 10 years using a Markov-based microsimulation model. The obese population examined is nationally representative of obese adults in the US from the 2005-2012 National Health and Nutrition Examination Surveys, while a matched normal weight population was constructed to have similar demographics as the obese population during the same period. Prediction equations for onset of obesity-related comorbidities, medical expenditures, economic outcomes, mortality, and quality-of-life came from published trials and studies supplemented with original research. Model validation followed International Society for Pharmacoeconomics and Outcomes Research practice guidelines. Among surviving adults, relative to a matched normal weight population, obese adults averaged $3900 higher medical expenditures in the initial year, growing to $4600 higher expenditures in year 10. Obese adults had higher initial prevalence and higher simulated onset of comorbidities as they aged. Over 10 years, excess medical expenditures attributed to obesity averaged $4280 annually-ranging from $2820 for obese category I to $5100 for obese category II, and $8710 for obese category III. Each excess kilogram of weight contributed to $140 higher annual costs, on average, ranging from $136 (obese I) to $152 (obese III). Poor health associated with obesity increased work absenteeism and mortality, and lowered employment probability, personal income, and quality-of-life. This validated model helps illustrate why obese adults have higher medical and indirect costs relative to normal weight adults, and shows that medical costs

Obesity Stigma: Important Considerations for Public Health

PubMed Central

Heuer, Chelsea A.

2010-01-01

Stigma and discrimination toward obese persons are pervasive and pose numerous consequences for their psychological and physical health. Despite decades of science documenting weight stigma, its public health implications are widely ignored. Instead, obese persons are blamed for their weight, with common perceptions that weight stigmatization is justifiable and may motivate individuals to adopt healthier behaviors. We examine evidence to address these assumptions and discuss their public health implications. On the basis of current findings, we propose that weight stigma is not a beneficial public health tool for reducing obesity. Rather, stigmatization of obese individuals threatens health, generates health disparities, and interferes with effective obesity intervention efforts. These findings highlight weight stigma as both a social justice issue and a priority for public health. PMID:20075322

Therapeutic interventions for hypertension in metabolic syndrome: a comprehensive approach.

PubMed

Ganne, Sudha; Arora, Surender; Karam, Jocelyne; McFarlane, Samy I

2007-03-01

Hypertension is a major component of the metabolic syndrome and a major cardiovascular risk factor. Both disorders are rapidly increasing in frequency, with hypertension affecting nearly 60 million Americans and over 1 billion people worldwide, and metabolic syndrome affecting 44% of the US population above the age of 60 years. Sedentary lifestyle, together with obesity and aging of the population, are the major contributing factors for this growing epidemic. Hypertension in metabolic syndrome possesses unique pathophysiological aspects that have considerable implications on therapy of this disease. In this article, we review the pathophysiology and provide a rationale for the current therapeutic options in light of the most recent clinical trials in the field.

Dynamic Model Predicting Overweight, Obesity, and Extreme Obesity Prevalence Trends

PubMed Central

Thomas, Diana M.; Weedermann, Marion; Fuemmeler, Bernard F.; Martin, Corby K.; Dhurandhar, Nikhil V.; Bredlau, Carl; Heymsfield, Steven B.; Ravussin, Eric; Bouchard, Claude

2013-01-01

Objective Obesity prevalence in the United States (US) appears to be leveling, but the reasons behind the plateau remain unknown. Mechanistic insights can be provided from a mathematical model. The objective of this study is to model known multiple population parameters associated with changes in body mass index (BMI) classes and to establish conditions under which obesity prevalence will plateau. Design and Methods A differential equation system was developed that predicts population-wide obesity prevalence trends. The model considers both social and non-social influences on weight gain, incorporates other known parameters affecting obesity trends, and allows for country specific population growth. Results The dynamic model predicts that: obesity prevalence is a function of birth rate and the probability of being born in an obesogenic environment; obesity prevalence will plateau independent of current prevention strategies; and the US prevalence of obesity, overweight, and extreme obesity will plateau by about 2030 at 28%, 32%, and 9%, respectively. Conclusions The US prevalence of obesity is stabilizing and will plateau, independent of current preventative strategies. This trend has important implications in accurately evaluating the impact of various anti-obesity strategies aimed at reducing obesity prevalence. PMID:23804487

Implications of life-history strategies for obesity

PubMed Central

Maner, Jon K.; Dittmann, Andrea; Meltzer, Andrea L.; McNulty, James K.

2017-01-01

The association between low socioeconomic status (SES) and obesity is well documented. In the current research, a life history theory (LHT) framework provided an explanation for this association. Derived from evolutionary behavioral science, LHT emphasizes how variability in exposure to unpredictability during childhood gives rise to individual differences in a range of social psychological processes across the life course. Consistent with previous LHT research, the current findings suggest that exposure to unpredictability during childhood (a characteristic common to low SES environments) is associated with the adoption of a fast life-history strategy, one marked by impulsivity and a focus on short-term goals. We demonstrate that a fast life-history strategy, in turn, was associated with dysregulated weight-management behaviors (i.e., eating even in the absence of hunger), which were predictive of having a high body mass index (BMI) and being obese. In both studies, findings held while controlling for participants’ current socioeconomic status, suggesting that obesity is rooted in childhood experiences. A serial mediation model in study 2 confirmed that effects of childhood SES on adult BMI and obesity can be explained in part by exposure to unpredictability, the adoption of a fast life-history strategy, and dysregulated-eating behaviors. These findings suggest that weight problems in adulthood may be rooted partially in early childhood exposure to unpredictable events and environments. LHT provides a valuable explanatory framework for understanding the root causes of obesity. PMID:28739939

Lysine acetyltransferase inhibitors: structure-activity relationships and potential therapeutic implications.

PubMed

Fiorentino, Francesco; Mai, Antonello; Rotili, Dante

2018-05-01

Lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. The dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders. Many lysine acetyltransferase inhibitors (KATi) have been developed so far, but there is still the need for new, more potent, metabolically stable and selective KATi as chemical tools for studying KAT biology and/or as potential therapeutic agents. This review will examine the features of KAT enzymes and related diseases, with particular emphasis on KATi (bisubstrate analogs, natural compounds and synthetic derivatives), analyzing their mechanism of action, structure-activity relationships, pharmacokinetic/pharmacodynamic properties and potential future applications.

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

PubMed Central

Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

2013-01-01

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females

PubMed Central

Giles, Erin D.; Jackman, Matthew R.; MacLean, Paul S.

2016-01-01

Obesity is a worldwide epidemic, and the comorbidities associated with obesity are numerous. Over the last two decades, we and others have employed an outbred rat model to study the development and persistence of obesity, as well as the metabolic complications that accompany excess weight. In this review, we summarize the strengths and limitations of this model and how it has been applied to further our understanding of human physiology in the context of weight loss and weight regain. We also discuss how the approach has been adapted over time for studies in females and female-specific physiological conditions, such as menopause and breast cancer. As excess weight and the accompanying metabolic complications have become common place in our society, we expect that this model will continue to provide a valuable translational tool to establish physiologically relevant connections to the basic science studies of obesity and body weight regulation. PMID:27933296

Impaired Cardiolipin Biosynthesis Prevents Hepatic Steatosis and Diet-Induced Obesity

PubMed Central

Cole, Laura K.; Mejia, Edgard M.; Vandel, Marilyne; Sparagna, Genevieve C.; Claypool, Steven M.; Dyck-Chan, Laura; Klein, Julianne

2016-01-01

Mitochondria are the nexus of energy metabolism, and consequently their dysfunction has been implicated in the development of metabolic complications and progression to insulin resistance and type 2 diabetes. The unique tetra-acyl phospholipid cardiolipin (CL) is located in the inner mitochondrial membrane, where it maintains mitochondrial integrity. Here we show that knockdown of Tafazzin (TAZ kd), a CL transacylase, in mice results in protection against the development of obesity, insulin resistance, and hepatic steatosis. We determined that hypermetabolism protected TAZ kd mice from weight gain. Unexpectedly, the large reduction of CL in the heart and skeletal muscle of TAZ kd mice was not mirrored in the liver. As a result, TAZ kd mice exhibited normal hepatic mitochondrial supercomplex formation and elevated hepatic fatty acid oxidation. Collectively, these studies identify a key role for hepatic CL remodeling in regulating susceptibility to insulin resistance and as a novel therapeutic target for diet-induced obesity. PMID:27495222

Cell and molecular mechanisms behind diet-induced hypothalamic inflammation and obesity.

PubMed

Ávalos, Yenniffer; Kerr, Bredford; Maliqueo, Manuel; Dorfman, Mauricio

2018-04-12

Diet-induced obesity (DIO) is associated with chronic, low-grade inflammation in the hypothalamus, a key regulator of energy homeostasis. Current studies have revealed the involvement of different cell types as well as cell and molecular mechanisms that contribute to diet-induced hypothalamic inflammation (DIHI) and DIO. Since the discovery that high-fat diet and saturated fatty acids (SFAs) increase the expression of hypothalamic cytokines prior to weight gain, research has focused on understanding the cellular and molecular mechanisms underlying these changes, and what the role of inflammation in the obesity pathogenesis. Recent studies have proposed that the inhibition of proinflammatory pathways in microglia and astrocytes is sufficient to protect against DIHI and prevent obesity. In addition, impairment of intracellular and epigenetic mechanisms, such as hypothalamic autophagy and changes in the methylation pattern of certain genes, have been implicated in susceptibility to DIHI and DIO. Interestingly, a sexual dimorphism has been found during DIO in hypothalamic inflammation, glial activation and metabolic diseases, and recent data support an important role of sex steroids in DIHI. These new exciting findings uncover novel obesity pathogenic mechanisms and provide targets to develop therapeutic approaches. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Understanding High Incidence of Severe Obesity and Very Low Food Security in Food Pantry Clients: Implications For Social Work.

PubMed

Kaiser, Michelle L; Cafer, Anne

2018-01-01

The United States is facing two interconnected social and public health crises of severe obesity and food insecurity within the social-ecological environment. Marginalized groups experience the highest rates and the greatest impacts in terms of morbidity, mortality, and financial burdens. Consequences include experiencing multimorbidities, mental health issues, and decreased quality of life. Food pantries have served as spaces to obtain food to meet household needs, but for some, food pantries have become long-term solutions. We surveyed 2,634 people who accessed pantries in 2005, 2010, and 2013 across 32 counties in a Midwest state. The authors sought to understand to what extent does length of time using a food pantry, food security status, income sources, use of federal food benefits, visiting a doctor, and demographic variables increase odds of severe obesity. More than 14% were severely obese; those who were long-term food pantry users and very low food secure were 1.732 times more likely to be severely obese. Receiving Disability/Supplemental Security Income, seeing a doctor in the last year, being female, and older age reduced the odds of severe obesity. Discussion includes implications for social workers who interact with groups likely to experience very low food security and severe obesity at different systems levels.

Obesity, growth hormone and exercise.

PubMed

Thomas, Gwendolyn A; Kraemer, William J; Comstock, Brett A; Dunn-Lewis, Courtenay; Maresh, Carl M; Volek, Jeff S

2013-09-01

Growth hormone (GH) is regulated, suppressed and stimulated by numerous physiological stimuli. However, it is believed that obesity disrupts the physiological and pathological factors that regulate, suppress or stimulate GH release. Pulsatile GH has been potently stimulated in healthy subjects by both aerobic and resistance exercise of the right intensity and duration. GH modulates fuel metabolism, reduces total fat mass and abdominal fat mass, and could be a potent stimulus of lipolysis when administered to obese individuals exogenously. Only pulsatile GH has been shown to augment adipose tissue lipolysis and, therefore, increasing pulsatile GH response may be a therapeutic target. This review discusses the factors that cause secretion of GH, how obesity may alter GH secretion and how both aerobic and resistance exercise stimulates GH, as well as how exercise of a specific intensity may be used as a stimulus for GH release in individuals who are obese. Only five prior studies have investigated exercise as a stimulus of endogenous GH in individuals who are obese. Based on prior literature, resistance exercise may provide a therapeutic target for releasing endogenous GH in individuals who are obese if specific exercise programme variables are utilized. Biological activity of GH indicates that this may be an important precursor to beneficial changes in body fat and lean tissue mass in obese individuals. However, additional research is needed including what molecular GH variants are acutely released and involved at target tissues as a result of different exercise stimuli and what specific exercise programme variables may serve to stimulate GH in individuals who are obese.

Altered gas-exchange at peak exercise in obese adolescents: implications for verification of effort during cardiopulmonary exercise testing.

PubMed

Marinus, Nastasia; Bervoets, Liene; Massa, Guy; Verboven, Kenneth; Stevens, An; Takken, Tim; Hansen, Dominique

2017-12-01

Cardiopulmonary exercise testing is advised ahead of exercise intervention in obese adolescents to assess medical safety of exercise and physical fitness. Optimal validity and reliability of test results are required to identify maximal exercise effort. As fat oxidation during exercise is disturbed in obese individuals, it remains an unresolved methodological issue whether the respiratory gas exchange ratio (RER) is a valid marker for maximal effort during exercise testing in this population. RER during maximal exercise testing (RERpeak), and RER trajectories, was compared between obese and lean adolescents and relationships between RERpeak, RER slope and subject characteristics (age, gender, Body Mass Index [BMI], Tanner stage, physical activity level) were explored. Thirty-four obese (BMI: 35.1±5.1 kg/m²) and 18 lean (BMI: 18.8±1.9 kg/m²) adolescents (aged 12-18 years) performed a maximal cardiopulmonary exercise test on bike, with comparison of oxygen uptake (VO2), heart rate (HR), expiratory volume (VE), carbon dioxide output (VCO2), and cycling power output (W). RERpeak (1.09±0.06 vs. 1.14±0.06 in obese vs. lean adolescents, respectively) and RER slope (0.03±0.01 vs. 0.05±0.01 per 10% increase in VO2, in obese vs. lean adolescents, respectively) was significantly lower in obese adolescents, and independently related to BMI (P<0.05). Adjusted for HRpeak and VEpeak, RERpeak and RER slope remained significantly lower in obese adolescents (P<0.05). RER trajectories (in relation to %VO2peak and %Wpeak) were significantly different between groups (P<0.001). RERpeak is significantly lowered in obese adolescents. This may have important methodological implications for cardiopulmonary exercise testing in this population.

A Cognitive- Behavioral Therapeutic Program for Patients with Obesity and Binge Eating Disorder: Short- and Long- Term Follow-Up Data of a Prospective Study

ERIC Educational Resources Information Center

Vanderlinden, Johan; Adriaensen, An; Vancampfort, Davy; Pieters, Guido; Probst, Michel; Vansteelandt, Kristof

2012-01-01

The goal of this study is to investigate the efficacy of a manualized cognitive-behavioral therapeutic (CBT) approach for patients with obesity and binge eating disorder (BED) on the short and longer term. A prospective study without a control group consisting of three measurements (a baseline measurement and two follow-up assessments up to 5…

Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications

PubMed Central

Felger, Jennifer C.; Lotrich, Francis E.

2013-01-01

Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, e.g. brain derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression’s development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed. PMID:23644052

Targeting IFN-λ: therapeutic implications.

PubMed

Eslam, Mohammed; George, Jacob

2016-12-01

Type-III interferons (IFN-λ), the most recently discovered family of IFNs, shares common features with other family members, but also has many distinctive activities. IFN-λ uniquely has a different receptor complex, and a more focused pattern of tissue expression and signaling effects, from other classes of IFNs. Multiple genome-wide association studies (GWAS) and subsequent validation reports suggest a pivotal role for polymorphisms near the IFNL3 gene in hepatitis C clearance and control, as also for several other epithelial cell tropic viruses. Apart from its antiviral activity, IFN-λ possesses anti-tumor, immune-inflammatory and homeostatic functions. The overlapping effects of IFN-λ with type I IFN, with a restricted tissue expression pattern renders IFN-λ an attractive therapeutic target for viral infection, cancer and autoimmune diseases, with limited side effects. Areas covered: This review will summarize the current and future therapeutic opportunities offered by this most recently discovered family of interferons. Expert opinion: Our knowledge on IFN-λ is rapidly expanding. Though there are many remaining questions and challenges that require elucidation, the unique characteristics of IFN-λ increases enthusiasm that multiple therapeutic options will emerge.

Psychological aspects of obesity.

PubMed

Fabricatore, Anthony N; Wadden, Thomas A

2004-01-01

Obesity is a complex condition associated with a host of medical disorders. A common assumption is that obesity must also be related to psychological and emotional complications. Research on the psychosocial aspects of obesity has grown more sophisticated over the years, from purely theoretical papers to cross-sectional comparisons of people with and without obesity to prospective investigations of the temporal sequence of obesity and mood disturbance. These studies have shown that obesity, by itself, does not appear to be systematically associated with psychopathological outcomes. Certain obese individuals, however, are at greater risk of psychiatric disorder, especially depression. The present paper reviews the research findings and presents their clinical implications. Chiefly, treatment providers should not assume that a depressed or otherwise disturbed obese person needs only to lose weight in order to return to psychological health. Significant mood disturbances should be treated equally aggressively, regardless of a patient's weight status.

Role of Galectin-3 in Obesity and Impaired Glucose Homeostasis

PubMed Central

Menini, Stefano; Iacobini, Carla; Blasetti Fantauzzi, Claudia; Pesce, Carlo M.; Pugliese, Giuseppe

2016-01-01

Galectin-3 is an important modulator of several biological functions. It has been implicated in numerous disease conditions, particularly in the long-term complications of diabetes because of its ability to bind the advanced glycation/lipoxidation end products that accumulate in target organs and exert their toxic effects by triggering proinflammatory and prooxidant pathways. Recent evidence suggests that galectin-3 may also participate in the development of obesity and type 2 diabetes. It has been shown that galectin-3 levels are higher in obese and diabetic individuals and parallel deterioration of glucose homeostasis. Two studies in galectin-3 knockout mice fed a high-fat diet (HFD) have shown increased adiposity and adipose tissue and systemic inflammation associated with altered glucose homeostasis, suggesting that galectin-3 negatively modulates the responsiveness of innate and adaptive immunity to overnutrition. However, these studies have also shown that impaired glucose homeostasis occurs in galectin-3 knockout animals independently of obesity. Moreover, another study reported decreased weight and fat mass in HFD-fed galectin-3 knockout mice. In vitro, galectin-3 was found to stimulate differentiation of preadipocytes into mature adipocytes. Altogether, these data indicate that galectin-3 deserves further attention in order to clarify its role as a potential player and therapeutic target in obesity and type 2 diabetes. PMID:26770660

Building muscle, browning fat and preventing obesity by inhibiting myostatin.

PubMed

Lebrasseur, N K

2012-01-01

The obesity epidemic is an overwhelming global health concern. Interventions to improve body weight and composition aim to restore balance between nutrient intake and energy expenditure. Myostatin, a powerful negative regulator of skeletal muscle mass, has emerged as a potential therapeutic target for obesity and type 2 diabetes mellitus because of the prominent role skeletal muscle plays in metabolic rate and insulin-mediated glucose disposal. In fact, inhibition of myostatin by genetic manipulation or pharmacological means leads to a hypermuscular and very lean build in mice. The resistance of myostatin-null mice to diet-induced obesity, fat mass accumulation and metabolic dysfunction has been presumed to be a result of their large skeletal muscle mass; however, in this issue of Diabetologia, Zhang et al. (doi: 10.1007/s00125-011-2304-4 ) provide evidence that myostatin inhibition also significantly impacts the phenotype of white adipose tissue (WAT). The authors reveal elevated expression of key metabolic genes of fatty acid transport and oxidation and, intriguingly, the presence of brown adipose tissue-like cells in WAT of myostatin-null mice. They also show that pharmacological inhibition of myostatin replicates several of the protective benefits conveyed by its genetic inactivation. Herein, these data, areas in need of further investigation and the evidence that implicates myostatin as a target for obesity and type 2 diabetes mellitus are discussed.

Obese children experience higher plantar pressure and lower foot sensitivity than non-obese.

PubMed

da Rocha, Emmanuel Souza; Bratz, Denise Tiane Klein; Gubert, Larissa Colaço; de David, Ana; Carpes, Felipe P

2014-08-01

Children obesity is a risk factor for several dysfunctions and diseases, with negative effects on the morphology of the locomotor system, plantar pressure and body stability. A relationship between postural control and sensorimotor information has been assumed. However, there is few data on the effects of children obesity on the availability of sensorial information from the foot during standing. Twenty obese and twenty non-obese children were evaluated for foot sensitivity and plantar pressure during unipedal and bipedal stance. Data were compared between obese and non-obese participants, between foot regions and between legs. Obese children experiences higher plantar pressure and have lower foot sensitivity than non-obese. Additionally, obese children had similar sensitivity for different foot regions, as compared to the non-obese. Children obesity negatively influences foot sensitivity. Bipedal stance seemed more sensitive to differentiate between obese and non-obese. Higher plantar pressure and lower foot sensitivity in obese children may affect performance of weight bearing activities, contribute to higher risk of foot injuries and have potential implication for children footwear design and clinical physical examination. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implications of genome-wide association studies in cancer therapeutics.

PubMed

Patel, Jai N; McLeod, Howard L; Innocenti, Federico

2013-09-01

Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable. © 2013 The British Pharmacological Society.

Relational vulnerabilities of incarcerated and reentry mothers: therapeutic implications.

PubMed

Few-Demo, April L; Arditti, Joyce A

2014-11-01

A qualitative study involving a follow-up interview with 10 incarcerated and reentry mothers in rural southwest and central Virginia was conducted to explore the influence that women's close relationships have on their reentry experiences with their families. The Vulnerability Conceptual Model (VCM) was used to sensitize an examination of how incarcerated and reentry mothers negotiate relational vulnerabilities in the context of varying situational vulnerability. Grounded theory analysis revealed three themes that characterized relational vulnerabilities. Given our focus on close relationships and the potential of the VCM to identify opportunities for resilience and vulnerability, we highlighted the influence of ambiguous and ambivalent relationships and unresolved loss and grief due to relationship dissolution or the death of a parent, sibling, child, or intimate partner in the reentry process. The data revealed two types of reentry mothers with divergent trajectories for social reintegration. Implications of these types for therapeutic treatment approaches for reentry women are discussed. © The Author(s) 2013.

Obesity in America: implications for clinical and health psychologists.

PubMed

Bean, Melanie K; Stewart, Karen; Olbrisch, Mary Ellen

2008-09-01

The number of individuals classified as overweight and obese is increasing at alarming rates and these conditions are associated with numerous psychological and physiological health problems. Within this epidemic, there is an increasing need and demand for psychologists and other mental health professionals to participate in the care of patients with obesity, both in assessment and treatment domains. The current paper provides a review of the status of the obesity epidemic, including psychological comorbidities and treatment approaches. Throughout this review, we highlight and discuss the important roles and impact psychologists can have. These roles include serving as members of multidisciplinary obesity treatment programs, conducting assessments for bariatric surgery, and treating related psychiatric disorders, such as depression and disordered eating. Other considerations, such as weight gain associated with psychiatric medications, and directions for future involvement of psychologists in addressing the obesity epidemic are also discussed.

Linking obesity and asthma.

PubMed

Sutherland, E Rand

2014-04-01

A growing body of literature suggests that obesity has a significant impact on asthma risk, phenotype, and prognosis. Epidemiological studies have clearly demonstrated that asthma is more likely to occur in obese patients, and health status is impaired in obese individuals with asthma, with obese asthmatics experiencing more symptoms, worse quality of life, increased healthcare use, and increased asthma severity. However, obesity has well-described effects on lung function and mechanics that can lead to symptoms of dyspnea without causing the pathophysiologic changes of asthma. Adding to the challenges of evaluating this association, some studies have failed to demonstrate a robust relationship between obesity and traditional biomarkers of airway inflammation in adult asthmatics, leading to the conclusion that obesity does not necessarily worsen airway inflammation in asthma. In this regard, emerging data suggest that nonatopic mechanisms may be relevant in obese asthmatics, and that these mechanisms may have a direct impact on the response of obese asthmatics to asthma therapies, most notably inhaled glucocorticoids. This article will review selected aspects of the contributions of obesity-related airway and systemic inflammation to asthma, with a focus on the impact of obesity as a modifier of risk, prognosis, and therapeutic response in asthma. © 2014 New York Academy of Sciences.

[The personality of obese persons in psychological tests with special consideration on latent obesity].

PubMed

Pudel, V; Metzdorff, M; Oetting, M

1975-01-01

The results of psychological tests of the obese are inconsistent and no characteristic personality structure of the obese can be deduced from them. Investigations in childhood obesity failed to establish a general psychogenetic model of obesity. Yet overweight and ideal weight-subjects differ in spontaneous eating behaviour. Appetite and satiety of obese subjects are controlled by external stimuli to a far greater extent than in nonobese. From a behavioural scientific viewpoint it is proposed that learning experiences during childhood socialisation generate the disposition for obesity which can manifest itself later, after interaction with a special environment. At this stage, however, individual reactions to starting overweight are insolved; this process is strongly influenced by individual personality structures: an inadequate conflict management favours obesity; by cognitive control normal weight can be preserved in spite of the acquired disposition for obesity. Taking these "latently obese" as an example the role of personality structure and wrong eating habits is discussed and related to possible therapeutic strategies. A model of the psychogenetic basis of obesity is proposed. In this model eating-related learning experience is attributed a primary role and individual personality structure a secondary role in the psychogenesis of obesity.

Biology of obesity and weight regain: Implications for clinical practice.

PubMed

Rogge, Mary Madeline; Gautam, Bibha

2017-10-01

Weight loss is recommended as first-line therapy for many chronic illnesses, including obesity. Most patients who do successfully lose weight are unable to maintain their reduced weight. Recent research findings are reviewed and synthesized to explain the biology of obesity, adaptation to weight loss, and weight regain. Weight regain is a common consequence of successful weight loss. Current obesity management strategies fail to take into consideration the underlying genetic and environmental causes of obesity. Available treatment modalities create a negative energy balance that stimulates integrated, persistent neurologic, endocrine, muscle, and adipose tissue adaptation to restore body weight and fat mass, independent of lifestyle changes. Understanding the pathophysiology of obesity and weight loss alters nurse practitioners' responsibilities in caring for patients with obesity. They are responsible for expanding assessment and intervention strategies and offering people with obesity realistic expectations for weight loss and regain. They are obligated to explain weight regain when it occurs to minimize patient frustration. Nurse practitioners have the opportunity to adopt new approaches to patient advocacy, especially in the areas of public policy to improve diagnostic tools and adjunctive therapy for people with obesity. ©2017 American Association of Nurse Practitioners.

Mature aggressive B-cell lymphoma across age groups - molecular advances and therapeutic implications.

PubMed

Lange, Jonas; Lenz, Georg; Burkhardt, Birgit

2017-02-01

Mature B-cell lymphoma represents the most common type of Non-Hodgkin lymphoma, and different subtypes prevail at different patient ages. Areas covered: We review recent data on differences and commonalities in mature B-cell lymphoma occurring in adult and pediatric patients, with a special emphasis on molecular advances and therapeutic implications. To this end, we will discuss knowledge on diffuse large B-cell lymphoma and Burkitt lymphoma/leukemia, which are the most frequent subtypes in adult and pediatric patients, respectively, and on primary mediastinal B-cell lymphoma, which is a subtype of mature B-cell lymphoma occurring mainly in adolescents and young adults with a female predominance. Expert commentary: Molecular profiling has revealed molecular alterations that can be used to further classify the subtypes of mature B-cell lymphoma. These new subgroups frequently respond differentially to targeted therapeutic strategies. Future clinical trials utilizing new drugs will address this issue by combining clinical data and response assessment with a molecular workup of the corresponding lymphomas.

Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88.

PubMed

Castoldi, Angela; Andrade-Oliveira, Vinicius; Aguiar, Cristhiane Favero; Amano, Mariane Tami; Lee, Jennifer; Miyagi, Marcelli Terumi; Latância, Marcela Teatin; Braga, Tarcio Teodoro; da Silva, Marina Burgos; Ignácio, Aline; Carola Correia Lima, Joanna Darck; Loures, Flavio V; Albuquerque, José Antonio T; Macêdo, Marina Barguil; Almeida, Rafael Ribeiro; Gaiarsa, Jonas W; Luévano-Martínez, Luis A; Belchior, Thiago; Hiyane, Meire Ioshie; Brown, Gordon D; Mori, Marcelo A; Hoffmann, Christian; Seelaender, Marília; Festuccia, Willian T; Moraes-Vieira, Pedro Manoel; Câmara, Niels Olsen Saraiva

2017-06-13

The underlying mechanism by which MyD88 regulates the development of obesity, metainflammation, and insulin resistance (IR) remains unknown. Global deletion of MyD88 in high-fat diet (HFD)-fed mice resulted in increased weight gain, impaired glucose homeostasis, elevated Dectin-1 expression in adipose tissue (AT), and proinflammatory CD11c+ AT macrophages (ATMs). Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR and had reduced CD11c+ AT macrophages. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ AT macrophages in chow- and HFD-fed MyD88 KO mice. Dectin-1 agonist worsened glucose homeostasis in MyD88 KO mice. Dectin-1 expression is increased in AT from obese individuals. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ AT macrophages in the absence of MyD88 and identify a role for Dectin-1 in chronic inflammatory states, such as obesity. This suggests that Dectin-1 may have therapeutic implications as a biomarker for metabolic dysregulation in humans. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Discordant signaling and autophagy response to fasting in hearts of obese mice: Implications for ischemia tolerance

PubMed Central

Kooren, Joel A.; Parker, Sarah J.; Tucker, Kyle C.; Ravindran, Nandini; Ito, Bruce R.; Huang, Chengqun; Venkatraman, Vidya; Van Eyk, Jennifer E.; Gottlieb, Roberta A.; Mentzer, Robert M.

2016-01-01

Autophagy is regulated by nutrient and energy status and plays an adaptive role during nutrient deprivation and ischemic stress. Metabolic syndrome (MetS) is a hypernutritive state characterized by obesity, dyslipidemia, elevated fasting blood glucose levels, and insulin resistance. It has also been associated with impaired autophagic flux and larger-sized infarcts. We hypothesized that diet-induced obesity (DIO) affects nutrient sensing, explaining the observed cardiac impaired autophagy. We subjected male friend virus B NIH (FVBN) mice to a high-fat diet, which resulted in increased weight gain, fat deposition, hyperglycemia, insulin resistance, and larger infarcts after myocardial ischemia-reperfusion. Autophagic flux was impaired after 4 wk on a high-fat diet. To interrogate nutrient-sensing pathways, DIO mice were subjected to overnight fasting, and hearts were processed for biochemical and proteomic analysis. Obese mice failed to upregulate LC3-II or to clear p62/SQSTM1 after fasting, although mRNA for LC3B and p62/SQSTM1 were appropriately upregulated in both groups, demonstrating an intact transcriptional response to fasting. Energy- and nutrient-sensing signal transduction pathways [AMPK and mammalian target of rapamycin (mTOR)] also responded appropriately to fasting, although mTOR was more profoundly suppressed in obese mice. Proteomic quantitative analysis of the hearts under fed and fasted conditions revealed broad changes in protein networks involved in oxidative phosphorylation, autophagy, oxidative stress, protein homeostasis, and contractile machinery. In many instances, the fasting response was quite discordant between lean and DIO mice. Network analysis implicated the peroxisome proliferator-activated receptor and mTOR regulatory nodes. Hearts of obese mice exhibited impaired autophagy, altered proteome, and discordant response to nutrient deprivation. PMID:27199111

Land-based versus aquatic resistance therapeutic exercises for older women with sarcopenic obesity: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Sarcopenic obesity is a health condition that combines excess adipose tissue and loss of muscle mass and strength. Sarcopenic obesity predisposes to more functional disabilities than obesity or sarcopenia alone. Progressive resistance exercises are recommended for older people as a potential treatment for sarcopenia and also for obesity. However, there is a lack of evidence indicating which programmes are best applied to older people, and no studies have investigated their effects on sarcopenic obese people. The aims of this protocol study are to investigate and compare the efficacy of land-based and aquatic resistance exercise programmes on improving muscle performance, functional capacity and quality of life of older women with sarcopenic obesity. Methods/Design This is a protocol study for a parallel randomised controlled clinical trial. Eligible participants are older women (≥65 years) with a body mass index ≥30 kg/m 2 and hand grip strength ≤21 kg force. A total sample of 36 participants will be randomly allocated to one of the intervention groups in blocks of three: land-based, aquatic or control. Each intervention group will undergo 2-week sessions of a 10-week therapeutic exercise programme for strength, power and endurance training of the lower-limb muscles. Participants in the control group will not participate in any strengthening activity for lower limbs and will receive telephone calls once a week. Baseline and final evaluation of outcomes will encompass muscle performance of the lower limbs assessed by an isokinetic dynamometer; functional tests of usual walking speed, maximal walking speed (shuttle walking test), stair speed and the Short Physical Performance Battery; and health-related quality of life (Medical Outcomes Study Short Form Questionnaire – SF-36). Data collectors will be blinded to randomisation and will not be in touch with participants during the interventions. Discussion This study is the first randomised controlled

SULF2 strongly prediposes to fasting and postprandial triglycerides in patients with obesity and type 2 diabetes mellitus.

PubMed

Hassing, H Carlijne; Surendran, R Preethi; Derudas, Bruno; Verrijken, An; Francque, Sven M; Mooij, Hans L; Bernelot Moens, Sophie J; Hart, Leen M 't; Nijpels, Giel; Dekker, Jacqueline M; Williams, Kevin Jon; Stroes, Erik S G; Van Gaal, Luc F; Staels, Bart; Nieuwdorp, Max; Dallinga-Thie, Geesje M

2014-05-01

Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM. Copyright © 2013 The Obesity Society.

Obesity and kidney protection

PubMed Central

Chandra, Aravind; Biersmith, Michael; Tolouian, Ramin

2014-01-01

Context: Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. Results: The concept of the “Metabolic Syndrome“ helps us to understand this close link between obesity, diabetes, hypertension, and renal dysfunction. An elevated body mass index has shown to be one of the major determinants of glomerular hyperfiltration that lead to the development of chronic kidney disease. Interestingly, weight loss can lead to attenuation of hyperfiltration in severely obese patients suggesting a possible therapeutic option to combat obesity-related hyperfiltration. Conclusions: Various treatment strategies had been suggested to decrease impact of obesity on kidneys. These are blood pressure controling, inhibition of the renin-angiotensinaldosterone axis, improving glycemic control, improving dyslipidemia, improving protein uriaand lifestyle modifications. Regardless of the numerous pharmacotherapies, the focus should be on the root cause: obesity. PMID:25093156

Obesity and kidney protection.

PubMed

Chandra, Aravind; Biersmith, Michael; Tolouian, Ramin

2014-07-01

Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. The concept of the "Metabolic Syndrome" helps us to understand this close link between obesity, diabetes, hypertension, and renal dysfunction. An elevated body mass index has shown to be one of the major determinants of glomerular hyperfiltration that lead to the development of chronic kidney disease. Interestingly, weight loss can lead to attenuation of hyperfiltration in severely obese patients suggesting a possible therapeutic option to combat obesity-related hyperfiltration. Various treatment strategies had been suggested to decrease impact of obesity on kidneys. These are blood pressure controling, inhibition of the renin-angiotensinaldosterone axis, improving glycemic control, improving dyslipidemia, improving protein uriaand lifestyle modifications. Regardless of the numerous pharmacotherapies, the focus should be on the root cause: obesity.

The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity

PubMed Central

Nielsen, Louise Aas; Nielsen, Tenna Ruest Haarmark; Holm, Jens-Christian

2015-01-01

The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring. PMID:26465142

[Gut microbiota: Description, role and pathophysiologic implications].

PubMed

Landman, C; Quévrain, E

2016-06-01

The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Lorcaserin Hcl for the treatment of obesity.

PubMed

Shukla, Alpana P; Kumar, Rekha B; Aronne, Louis J

2015-01-01

Obesity is a major health priority necessitating safe and effective strategies to address the obesity epidemic. Lorcaserin is a serotonergic agonist specific to the 5HT- 2C receptor approved for chronic management of obesity in patients with a BMI ≥ 30 kg/m(2) or a BMI ≥ 27 kg/m(2) with comorbidities related to obesity. In this paper, the pharmacodynamic and pharmacokinetic properties of lorcaserin are reviewed followed by a discussion of efficacy and safety data from major clinical trials. Lorcaserin is a unique highly selective serotonergic agonist designed to mitigate the risks associated with previous agents in this class. At therapeutic doses, it is well tolerated and produces modest but clinically meaningful weight loss with significant improvement in cardiometabolic parameters. Therapeutic efficacy should be assessed at 12 weeks (≥ 5% weight loss) to identify responders who will derive maximum weight loss and metabolic benefit from long-term therapy. The results of the ongoing cardiovascular outcomes trial (CAMELLIA TIMI 61) will determine the role of lorcaserin in primary prevention of diabetes in overweight/obese individuals and its use in the high-risk population of patients with established cardiovascular disease or multiple cardiovascular risk factors.

Decreased expression of CD36 in circumvallate taste buds of high-fat diet induced obese rats.

PubMed

Zhang, Xiao-Juan; Zhou, Li-Hong; Ban, Xiang; Liu, Dian-Xin; Jiang, Wei; Liu, Xiao-Min

2011-10-01

Mammals spontaneously prefer lipid rich foods. Overconsumption of high-fat diet leads to obesity and related diseases. Recent findings indicate that taste may participate in the orosensory perception of dietary lipids and the fatty taste may contribute to a preference for and excessive consumption of dietary fat. CD36, a trans-membrane glycoprotein, which is located in the taste buds of circumvallate papillae of rodents, appears to be a plausible receptor for this fatty taste. Obese subjects present a stronger preference for fatty foods, though the mechanisms involved are complex and are not fully investigated. Our data from immunofluorescence and real-time RT-PCR showed that the expression levels of CD36 in circumvallate taste buds were significantly lower in high-fat diet induced obese rats as compared with that of control rats fed a normal diet. These results suggest that decreased expression of CD36 in circumvallate taste buds of high-fat diet induced obese rats may be associated with diminished fatty taste sensitivity and in order to compensate the preference for dietary fat, rats consume more fatty foods. Therapeutic strategies designed to alter or manipulate CD36 expression or function in taste buds may have important implications in treating obesity and related diseases. Copyright © 2010 Elsevier GmbH. All rights reserved.

Vitamin D and obesity.

PubMed

Vanlint, Simon

2013-03-20

Obesity is a significant health problem world-wide, particularly in developed nations. Vitamin D deficiency is pandemic, and has been implicated in a wide variety of disease states. This paper seeks to examine the consistently reported relationship between obesity and low vitamin D concentrations, with reference to the possible underlying mechanisms. The possibility that vitamin D may assist in preventing or treating obesity is also examined, and recommendations for future research are made. There is a clear need for adequately-powered, prospective interventions which include baseline measurement of 25D concentrations and involve adequate doses of supplemental vitamin D. Until such studies have been reported, the role of vitamin D supplementation in obesity prevention remains uncertain.

The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications.

PubMed

Sundararajan, Vignesh; Sarkar, Fazlul H; Ramasamy, Thamil Selvee

2018-06-01

Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules. This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel

Ciliary dysfunction and obesity.

PubMed

Mok, C A; Héon, E; Zhen, M

2010-01-01

Obesity associates with increased health risks such as heart disease, stroke and diabetes. The steady rise in the obese population worldwide poses an increasing burden on health systems. Genetic factors contribute to the development of obesity, and the elucidation of their physiological functions helps to understand the cause, and improve the prevention, diagnosis and treatment for this disorder. Primary cilia are evolutionarily conserved organelles whose dysfunctions lead to human disorders now defined as ciliopathies. Human ciliopathies present pleiotropic and overlapping phenotypes that often include retinal degeneration, cystic renal anomalies and obesity. Increasing evidence implicates an intriguing involvement of cilia in lipid/energy homeostasis. Here we discuss recent studies in support of the key roles of ciliary genes in the development and pathology of obesity in various animal models. Genes affecting ciliary development and function may pose promising candidate underlying genetic factors that contribute to the development of common obesity.

Obesity and people with disabilities: the implications for health care expenditures.

PubMed

Anderson, Wayne L; Wiener, Joshua M; Khatutsky, Galina; Armour, Brian S

2013-12-01

This study estimates additional average health care expenditures for overweight and obesity for adults with disabilities vs. without. Descriptive and multivariate methods were used to estimate additional health expenditures by service type, age group, and payer using 2004-2007 Medical Expenditure Panel Survey data. In 2007, 37% of community-dwelling Americans with disabilities were obese vs. 27% of the total population. People with disabilities had almost three times ($2,459) the additional average obesity cost of people without disabilities ($889). Prescription drug expenditures for obese people with disabilities were three times as high and outpatient expenditures were 74% higher. People with disabilities in the 45- to 64-year age group had the highest obesity expenditures. Medicare had the highest additional average obesity expenditures among payers. Among people with prescription drug expenditures, obese people with disabilities had nine times the prevalence of diabetes as normal weight people with disabilities. Overweight people with and without disabilities had lower expenditures than normal-weight people with and without disabilities. Obesity results in substantial additional health care expenditures for people with disabilities. These additional expenditures pose a serious current and future problem, given the potential for higher obesity prevalence in the coming decade. Copyright © 2013 The Obesity Society.

IV. The cognitive implications of obesity and nutrition in childhood.

PubMed

Khan, Naiman A; Raine, Lauren B; Donovan, Sharon M; Hillman, Charles H

2014-12-01

The prevalence of childhood obesity in the United States has tripled since the 1980s and is strongly linked to the early onset of several metabolic diseases. Recent studies indicate that lower cognitive function may be another complication of childhood obesity. This review considers the research to date on the role of obesity and nutrition on childhood cognition and brain health. Although a handful of studies point to a maladaptive relationship between obesity and aspects of cognitive control, remarkably little is known regarding the impact of fat mass on brain development and cognitive function. Further, missing from the literature is the role of nutrition in the obesity-cognition interaction. Nutrition may directly or indirectly influence cognitive performance via several pathways including provision of key substrates for optimal brain health, modulation of gut microbiota, and alterations in systemic energy balance. However, in the absence of malnutrition, the functional benefits of specific nutrient intake on particular cognitive domains are not well characterized. Here, we examine the literature linking childhood obesity and cognition while considering the effects of nutritional intake. Possible mechanisms for these relationships are discussed and suggestions are made for future study topics. Although childhood obesity prevalence rates in some developed countries have recently stabilized, significant disparities remain among groups based on sex and socioeconomic status. Given that the elevated prevalence of pediatric overweight and obesity may persist for the foreseeable future, it is crucial to develop a comprehensive understanding of the influence of obesity and nutrition on cognition and brain health in the pediatric population. © 2014 The Society for Research in Child Development, Inc.

Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure.

PubMed

Lavie, Carl J; Alpert, Martin A; Arena, Ross; Mehra, Mandeep R; Milani, Richard V; Ventura, Hector O

2013-04-01

Obesity has reached epidemic proportions in the United States and worldwide. Considering the adverse effects of obesity on left ventricular (LV) structure, diastolic and systolic function, and other risk factors for heart failure (HF), including hypertension and coronary heart disease, HF incidence and prevalence, not surprisingly, is markedly increased in obese patients. Nevertheless, as with most other cardiovascular diseases, numerous studies have documented an obesity paradox, in which overweight and obese patients, defined by body mass index, percent body fat, or central obesity, demonstrate a better prognosis compared with lean or underweight HF patients. This review will describe the data on obesity in the context of cardiopulmonary exercise testing in HF. Additionally, the implications of obesity on LV assist devices and heart transplantation are reviewed. Finally, despite the obesity paradox, we address the current state of weight reduction in HF. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus

PubMed Central

Hassing, H. Carlijne; Surendran, R. Preethi; Derudas, Bruno; Verrijken, An; Francque, Sven M.; Mooij, Hans L.; Bernelot Moens, Sophie J.; ’t Hart, Leen M.; Nijpels, Giel; Dekker, Jacqueline M.; Williams, Kevin Jon; Stroes, Erik S. G.; Van Gaal, Luc F.; Staels, Bart; Nieuwdorp, Max; Dallinga-Thie, Geesje M.

2014-01-01

Objective Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodelling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here we sought to investigate the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM. Design and Methods Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Results Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; p=0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (p<0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P<0.05) and retinyl esters (RE) levels (P<0.001). Conclusions These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM. PMID:24339435

FAT-FREE MASS, METABOLICALLY HEALTHY OBESITY, AND TYPE 2 DIABETES IN SEVERELY OBESE ASIAN ADULTS.

PubMed

Pramyothin, Pornpoj; Limpattanachart, Vichol; Dawilai, Suwitcha; Sarasak, Rungnapha; Sukaruttanawong, Chariya; Chaiyasoot, Kusuma; Keawtanom, Songsri; Yamwong, Preyanuj

2017-08-01

To determine whether fat free mass (FFM) is independently associated with the metabolically healthy obesity (MHO) phenotype, the metabolic syndrome (MS), and type 2 diabetes (T2D) in obese Asian adults. Obese patients (body mass index [BMI] ≥25 kg/m 2 ) seeking weight management at an academic medical center from 2007 to 2016 were included. FFM was measured by bioelectrical impedance. Of the 552 patients (67.0% female, median age 40.5 years, median BMI 38.3 kg/m 2 ), MHO was present in 19%, MS in 55.4%, and T2D in 32.6%. In multivariate models, higher fat-free mass index (FFMI) was independently associated with the metabolically abnormal obesity (MAO) phenotype, (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.09-1.37), and increased risk of MS (OR 1.12, 95% CI 1.03-1.22) in women but not in men. Older age was independently associated with the MAO phenotype (OR 1.06, 95% CI 1.04-1.09 in women; OR 1.06, 95% CI 1.02-1.09 in men), MS (OR 1.05, 95% CI 1.03-1.06 in women; OR 1.05, 95% CI 1.02-1.07 in men), and T2D (OR 1.07, 95% CI 1.05-1.09 in women; OR 1.06, 95% CI 1.04-1.09 in men). Waist-hip ratio was independently associated with the MAO phenotype in men (OR 1.08, 95% CI 1.01-1.15), while waist circumference was associated with T2D in women (OR 1.03, 95% CI 1.01-1.05). Older age, central fat distribution, and-in contrast to previous findings-an increase in FFMI among women were independent predictors of adverse metabolic health in this cohort of middle-aged obese Asian adults. Further studies are required to elucidate underlying mechanisms and therapeutic implications of these findings. BIA = bioelectrical impedance analysis BMI = body mass index CI = confidence interval DXA = dual-energy X-ray absorptiometry FFM = fat-free mass FFMI = fat-free mass index FM = fat mass HbA1c = glycated hemoglobin A1c MAO = metabolically abnormal obesity MHO = metabolically healthy obesity MS = metabolic syndrome OR = odds ratio T2D = type 2 diabetes WC = waist circumference

Trans-anethole ameliorates obesity via induction of browning in white adipocytes and activation of brown adipocytes.

PubMed

Kang, Nam Hyeon; Mukherjee, Sulagna; Min, Taesun; Kang, Sun Chul; Yun, Jong Won

2018-05-24

To treat obesity, suppression of white adipose tissue (WAT) expansion and activation of brown adipose tissue (BAT) are considered as potential therapeutic targets. Recent advances have been made in the induction of brown fat-like adipocytes (beige) in WAT, which represents an attractive potential strategy for the management and treatment of obesity. Use of natural compounds for browning of white adipocytes can be considered as a safe and novel strategy against obesity. Here, we report that trans-anethole (TA), a flavoring substance present in the essential oils of various plants, alleviated high fat diet (HFD)-induced obesity in mice models via elevation of the expression of beige-specific genes such as Ppargc1α, Prdm16, Ucp1, Cd137, Cited1, Tbx1, and Trem26. TA also regulated lipid metabolism in white adipocytes via reduction of adipogenesis and lipogenesis as well as elevation of lipolysis and fat oxidation. Moreover, TA exhibited thermogenic activity by increasing mitochondrial biogenesis in white adipocytes and activating brown adipocytes. In addition, molecular docking analysis enabled us to successfully predict core proteins for fat browning such as β3-adrenergic receptor (β3-AR) and sirtuin1 (SIRT1) based on their low binding energy interactions with TA for promotion of regulatory mechanisms. Indeed, agonistic and antagonistic studies demonstrated that TA induced browning of 3T3-L1 adipocytes through activation of β3-AR as well as the AMPK-mediated SIRT1 pathway regulating PPARα and PGC-1α. In conclusion, TA possesses potential therapeutic implications for treatment of obesity by playing multiple modulatory roles in the induction of white fat browning, activation of brown adipocytes, and promotion of lipid catabolism. Copyright © 2018. Published by Elsevier B.V.

TAM Receptors in Leukemia: Expression, Signaling, and Therapeutic Implications

PubMed Central

Brandão, Luis; Migdall-Wilson, Justine; Eisenman, Kristen; Graham, Douglas K.

2016-01-01

In the past 30 years there has been remarkable progress in the treatment of leukemia and lymphoma. However, current treatments are largely ineffective against relapsed leukemia and, in the case of pediatric patients, are often associated with severe long-term toxicities. Thus, there continues to be a critical need for the development of effective biologically targeted therapies. The TAM family of receptor tyrosine kinases—Tyro3, Axl, and Mer—plays an important role in normal hematopoiesis, including natural killer cell maturation, macrophage function, and platelet activation and signaling. Furthermore, TAM receptor activation leads to upregulation of pro-survival and proliferation signaling pathways, and aberrant TAM receptor expression contributes to cancer development, including myeloid and lymphoid leukemia. This review summarizes the role of TAM receptors in leukemia. We outline TAM receptor expression patterns in different forms of leukemia, describe potential mechanisms leading to their overexpression, and delineate the signaling pathways downstream of receptor activation that have been implicated in leukemogenesis. Finally, we discuss the current research focused on inhibitors against these receptors in an effort to develop new therapeutic strategies for leukemia. PMID:22150307

Discordant signaling and autophagy response to fasting in hearts of obese mice: Implications for ischemia tolerance.

PubMed

Andres, Allen M; Kooren, Joel A; Parker, Sarah J; Tucker, Kyle C; Ravindran, Nandini; Ito, Bruce R; Huang, Chengqun; Venkatraman, Vidya; Van Eyk, Jennifer E; Gottlieb, Roberta A; Mentzer, Robert M

2016-07-01

Autophagy is regulated by nutrient and energy status and plays an adaptive role during nutrient deprivation and ischemic stress. Metabolic syndrome (MetS) is a hypernutritive state characterized by obesity, dyslipidemia, elevated fasting blood glucose levels, and insulin resistance. It has also been associated with impaired autophagic flux and larger-sized infarcts. We hypothesized that diet-induced obesity (DIO) affects nutrient sensing, explaining the observed cardiac impaired autophagy. We subjected male friend virus B NIH (FVBN) mice to a high-fat diet, which resulted in increased weight gain, fat deposition, hyperglycemia, insulin resistance, and larger infarcts after myocardial ischemia-reperfusion. Autophagic flux was impaired after 4 wk on a high-fat diet. To interrogate nutrient-sensing pathways, DIO mice were subjected to overnight fasting, and hearts were processed for biochemical and proteomic analysis. Obese mice failed to upregulate LC3-II or to clear p62/SQSTM1 after fasting, although mRNA for LC3B and p62/SQSTM1 were appropriately upregulated in both groups, demonstrating an intact transcriptional response to fasting. Energy- and nutrient-sensing signal transduction pathways [AMPK and mammalian target of rapamycin (mTOR)] also responded appropriately to fasting, although mTOR was more profoundly suppressed in obese mice. Proteomic quantitative analysis of the hearts under fed and fasted conditions revealed broad changes in protein networks involved in oxidative phosphorylation, autophagy, oxidative stress, protein homeostasis, and contractile machinery. In many instances, the fasting response was quite discordant between lean and DIO mice. Network analysis implicated the peroxisome proliferator-activated receptor and mTOR regulatory nodes. Hearts of obese mice exhibited impaired autophagy, altered proteome, and discordant response to nutrient deprivation. Copyright © 2016 the American Physiological Society.

The relationship between emotional regulation and eating behaviour: a multidimensional analysis of obesity psychopathology.

PubMed

Micanti, Fausta; Iasevoli, Felice; Cucciniello, Claudia; Costabile, Raimondo; Loiarro, Giuseppe; Pecoraro, Giuseppe; Pasanisi, Fabrizio; Rossetti, GianLuca; Galletta, Diana

2017-03-01

The aim of this study is to show that the differences among eating behaviours are related to the emotional dysregulation connected to the mental dimensions being part of the obese psychopathology. Eating behaviours can be considered a diagnostic feature at the initial screening for determining the obesity treatment: nutritional or bariatric surgery. 1828 Obese subjects underwent psychiatric assessment before entering obesity nutritional treatment or bariatric surgery following the multidisciplinary programme. 1121 subjects were selected and enrolled in this study: 850 were inpatients visited or hospitalised at the Obesity Centre or at the Bariatric Surgery Units, 271 were outpatients visited at the Eating Disorder and Obesity Unit. Psychiatric examination was used to exclude psychiatric disorders and investigate eating behaviours distinguished on the basis of food intake rhythm in: gorging, snacking, grazing and binge. They are related to the mental dimensions: impulsiveness, body image, mood and anxiety, taking part in the emotional regulation system. Specific psychometric tools were used to investigate the different mental dimensions of the single eating behaviours and their differences. Statistical analysis of the psychopathological features was performed using ANOVA, ANCOVA, Levene test, Bonferroni's and Tamhane post hoc test. Significance was set at p < 0.05. Data analysis shows significant differences of psychopathology among all the eating behaviours and an increase in the emotional dysregulation determining maladaptive behaviours. Eating behaviours are connected to the balance of the different features of mental dimensions implicated in the emotional regulation system. They could provide significant clinical information and therefore be part of the obesity diagnostic criteria and therapeutic programme.

FTO associations with obesity and telomere length.

PubMed

Zhou, Yuling; Hambly, Brett D; McLachlan, Craig S

2017-09-01

This review examines the biology of the Fat mass- and obesity-associated gene (FTO), and the implications of genetic association of FTO SNPs with obesity and genetic aging. Notably, we focus on the role of FTO in the regulation of methylation status as possible regulators of weight gain and genetic aging. We present a theoretical review of the FTO gene with a particular emphasis on associations with UCP2, AMPK, RBL2, IRX3, CUX1, mTORC1 and hormones involved in hunger regulation. These associations are important for dietary behavior regulation and cellular nutrient sensing via amino acids. We suggest that these pathways may also influence telomere regulation. Telomere length (TL) attrition may be influenced by obesity-related inflammation and oxidative stress, and FTO gene-involved pathways. There is additional emerging evidence to suggest that telomere length and obesity are bi-directionally associated. However, the role of obesity risk-related genotypes and associations with TL are not well understood. The FTO gene may influence pathways implicated in regulation of TL, which could help to explain some of the non-consistent relationship between weight phenotype and telomere length that is observed in population studies investigating obesity.

Obesity and People with Disabilities: The Implications for Health Care Expenditures

PubMed Central

Anderson, Wayne L.; Wiener, Joshua M.; Khatutsky, Galina; Armour, Brian S.

2015-01-01

Objective This study estimates additional average health care expenditures for overweight and obesity for adults with disabilities vs. without. Design and Methods Descriptive and multivariate methods were used to estimate additional health expenditures by service type, age group, and payer using 2004–2007 Medical Expenditure Panel Survey data. Results In 2007, 37% of community-dwelling Americans with disabilities were obese vs. 27% of the total population. People with disabilities had almost three times ($2,459) the additional average obesity cost of people without disabilities ($889). Prescription drug expenditures for obese people with disabilities were three times as high and outpatient expenditures were 74% higher. People with disabilities in the 45- to 64-year age group had the highest obesity expenditures. Medicare had the highest additional average obesity expenditures among payers. Among people with prescription drug expenditures, obese people with disabilities had nine times the prevalence of diabetes as normal weight people with disabilities. Overweight people with and without disabilities had lower expenditures than normal-weight people with and without disabilities. Conclusions Obesity results in substantial additional health care expenditures for people with disabilities. These additional expenditures pose a serious current and future problem, given the potential for higher obesity prevalence in the coming decade. PMID:23804319

Vitamin D receptor signaling and its therapeutic implications: Genome-wide and structural view.

PubMed

Carlberg, Carsten; Molnár, Ferdinand

2015-05-01

Vitamin D3 is one of the few natural compounds that has, via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and the transcription factor vitamin D receptor (VDR), a direct effect on gene regulation. For efficiently applying the therapeutic and disease-preventing potential of 1,25(OH)2D3 and its synthetic analogs, the key steps in vitamin D signaling need to be understood. These are the different types of molecular interactions with the VDR, such as (i) the complex formation of VDR with genomic DNA, (ii) the interaction of VDR with its partner transcription factors, (iii) the binding of 1,25(OH)2D3 or its synthetic analogs within the ligand-binding pocket of the VDR, and (iv) the resulting conformational change on the surface of the VDR leading to a change of the protein-protein interaction profile of the receptor with other proteins. This review will present the latest genome-wide insight into vitamin D signaling, and will discuss its therapeutic implications.

7th to 9th grade obese adolescents' perceptions about obesity in Tamaulipas, Mexico.

PubMed

de la Luz Martínez-Aguilar, Ma; Flores-Peña, Yolanda; de las Mercedes Rizo-Baeza, Ma; Aguilar-Hernández, Rosa Ma; Vázquez-Galindo, Laura; Gutiérres-Sánchez, Gustavo

2010-01-01

The objective was to explore obese adolescents perceptions about obesity among students in the seventh to ninth grade of a public school in Tamaulipas, Mexico. This is a qualitative study. Participants were 24 adolescents with a body mass index equal to or greater than the 95th percentile. Semistructured interviews were conducted until data saturation was reached and the meaning was understood. The adolescents defined obesity according to standards of measurement. They identified the hereditary factor as the main obesity cause, tended to underestimate obesity and had low self-esteem. They reported problems to do physical exercise and get clothes in order to improve their image, and feel rejected by their peers in school. It was identified that these adolescents have psychological defense mechanisms against obesity and that some of them are making efforts to lose weight. Obesity entails social and psychological health implications for persons suffering from this problem. Interventions should be put in practice.

Challenges in obesity research.

PubMed

Palou, Andreu; Bonet, M Luisa

2013-09-01

Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Cardiovascular complications of obesity in adolescents.

PubMed

Orio, F; Palomba, S; Cascella, T; Savastano, S; Lombardi, G; Colao, A

2007-01-01

Obesity is an increasingly important worldwide health problem, representing the major risk factor for coronary heart disease. The increase in the prevalence of obesity, particularly among younger age groups, is likely to have long-term implications for cardiovascular disease (CVD) in the years to come, especially at a young age. Obesity plays a central role in the insulin resistance (IR) syndrome and increases the risk of atherosclerotic CVD. The present review will examine the relationships among cardiovascular risk (CVR) factors during the childhood-adolescence-adulthood transition. In fact, the relation between obesity, in particular visceral obesity and CVD, appears to develop at a relatively young age. The foremost physical consequence of obesity is atherosclerotic CVD, and an intriguing example of obesity-related cardiovascular complications affecting young women is the polycystic ovary syndrome (PCOS).

Prevalence of Obesity and Its Influence on Achievement of Cardiometabolic Therapeutic Goals in Chinese Type 2 Diabetes Patients: An Analysis of the Nationwide, Cross-Sectional 3B Study.

PubMed

Zhou, Xianghai; Ji, Linong; Ran, Xingwu; Su, Benli; Ji, Qiuhe; Pan, Changyu; Weng, Jianping; Ma, Changsheng; Hao, Chuanming; Zhang, Danyi; Hu, Dayi

2016-01-01

There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients. Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24-27.9 kg/m2 and ≥28.0 kg/m2. Central obesity was defined as a waist circumference ≥80 cm in women and ≥85 cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90 mmHg and LDL-C<2.6 mmol/L. Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and 10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals. Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients.

Obesity: modern man's fertility nemesis.

PubMed

Cabler, Stephanie; Agarwal, Ashok; Flint, Margot; du Plessis, Stefan S

2010-07-01

The obesity pandemic has grown to concerning proportions in recent years, not only in the Western World, but in developing countries as well. The corresponding decrease in male fertility and fecundity may be explained in parallel to obesity, and obesity should be considered as an etiology of male fertility. Studies show that obesity contributes to infertility by reducing semen quality, changing sperm proteomes, contributing to erectile dysfunction, and inducing other physical problems related to obesity. Mechanisms for explaining the effect of obesity on male infertility include abnormal reproductive hormone levels, an increased release of adipose-derived hormones and adipokines associated with obesity, and other physical problems including sleep apnea and increased scrotal temperatures. Recently, genetic factors and markers for an obesity-related infertility have been discovered and may explain the difference between fertile obese and infertile obese men. Treatments are available for not only infertility related to obesity, but also as a treatment for the other comorbidities arising from obesity. Natural weight loss, as well as bariatric surgery are options for obese patients and have shown promising results in restoring fertility and normal hormonal profiles. Therapeutic interventions including aromatase inhibitors, exogenous testosterone replacement therapy and maintenance and regulation of adipose-derived hormones, particularly leptin, may also be able to restore fertility in obese males. Because of the relative unawareness and lack of research in this area, controlled studies should be undertaken and more focus should be given to obesity as an etiolgy of male infertility.

Night eating syndrome: implications for severe obesity

PubMed Central

Cleator, J; Abbott, J; Judd, P; Sutton, C; Wilding, J P H

2012-01-01

Night eating syndrome (NES) was first identified in 1955 by Stunkard, a psychiatrist specialising in eating disorders (ED). Over the last 20 years considerable progress has been made in defining NES as a significant clinical entity in its own right and it has now been accepted for inclusion in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) due for publication in 2013. NES is considered a dysfunction of circadian rhythm with a disassociation between eating and sleeping. Core criteria include a daily pattern of eating with a significantly increased intake in the evening and/or night time, as manifested by one or both of the following: at least 25% of food intake is consumed after the evening meal or at least two episodes of nocturnal eating per week. An important recent addition to core criteria includes the presence of significant distress and/or impairment in functioning. Stunkard's team recommend further investigation on the pathogenesis of NES, in particular its relationship with traumatic life events, psychiatric comorbidity, the age of onset of NES and course of NES over time. The relationship between NES and other ED also requires further clarification as night-eaters exhibit some features of other ED; previous guidance to separate NES from other ED may have hindered earlier characterisation of NES. Evidence from European and American studies suggests NES features strongly in populations with severe obesity. The complex interplay between depression, impaired sleep and obesity-related comorbidity in severely obese individuals makes understanding NES in this context even more difficult. This review examines evidence to date on the characterisation of NES and concludes by examining the applicability of current NES criteria to individuals with severe obesity. PMID:23446659

Perception of stress and quality of life in overweight and obese people--implications for preventive consultancies in primary care.

PubMed

Metz, Ulrike; Welke, Justus; Esch, Tobias; Renneberg, Babette; Braun, Vittoria; Heintze, Christoph

2009-01-01

The increasing prevalence of obesity requires especially primary health care providers to act. General Practitioners (GP) in particular have the opportunity to motivate patients in early risk stages to follow weight reduction programmes before manifestation of associated diseases. In order to conduct preventive consultancies it is necessary to explore the individual physical and mental health status of patients. Aim of this study was to examine quality of life and perceived level of stress in overweight and obese patients treated in primary care. 123 patients, following a health Check up realized by their GP, rated self- reported questionnaires regarding quality of life and perceived level of stress (SF-12, PSS). Following descriptive analysis, differences in dependent variables related to BMI, sex and age were tested using ANOVA and regression analysis (SPSSv15.0). Restrictions in all parameters of mental health for overweight and obese patients in primary care were shown. Especially patients with a BMI above 30 kg/m2 reported a decreased level of quality of life. Health care providers should be aware of cumulative restrictions in mental health of their overweight patients. The findings provide essential implications for all health care professionals in primary care doing preventive consultancies with obese clients.

Multi-hormonal weight loss combinations in diet-induced obese rats: therapeutic potential of cholecystokinin?

PubMed

Trevaskis, James L; Turek, Victoria F; Griffin, Peter S; Wittmer, Carrie; Parkes, David G; Roth, Jonathan D

2010-05-11

Cholecystokinin (CCK) acutely synergizes with amylin to suppress food intake in lean mice. To extend on these findings, the present studies sought to identify neural correlates for the interaction of amylin and CCK, as well as further understand the therapeutic potential of CCK-based combinations in obesity. First, c-Fos activation was assessed in various brain nuclei after a single intraperitoneal injection of amylin (5microg/kg) and/or CCK (5microg/kg). Amylin and CCK additively increased c-Fos within the area postrema (AP), predominantly in noradrenergic (e.g., dopamine-beta-hydroxylase-containing) cells. Next, amylin (100 or 300microg/kg/d) and/or CCK (100 or 300microg/kg/d) were subcutaneously infused for 7days in diet-induced obese (DIO) rats. Amylin treatment of DIO rats for 7days induced significant body weight loss. CCK, while ineffective alone, significantly enhanced body weight loss when co-administered with the higher dose of amylin. Finally, the addition of CCK (300microg/kg/d) to leptin (125microg/kg/d), and to the combination of amylin (50microg/kg/d) and leptin (125microg/kg/d), was also explored in DIO rats via sustained subcutaneous infusion for 14days. Infusion of amylin/leptin/CCK for 14days exerted significantly greater body weight loss, inhibition of food intake, and reduction in adiposity compared to amylin/leptin treatment alone in DIO rats. However, co-infusion of CCK and leptin was an ineffective weight loss regimen in this model. Whereas CCK agonism alone is ineffective at eliciting or maintaining weight loss, it durably augmented the food intake and body weight-lowering effects of amylin and amylin/leptin in a relevant disease model, and when combined with amylin, cooperatively activated neurons within the caudal brainstem. Copyright 2010 Elsevier Inc. All rights reserved.

Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

PubMed

Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

2016-09-01

Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Obesity: Current and potential pharmacotherapeutics and targets.

PubMed

Narayanaswami, Vidya; Dwoskin, Linda P

2017-02-01

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed. Copyright © 2016 Elsevier

Obesity: Current and Potential Pharmacotherapeutics and Targets

PubMed Central

Narayanaswami, Vidya; Dwoskin, Linda P.

2016-01-01

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed. PMID:27773782

Stress-induced alterations in estradiol sensitivity increase risk for obesity in women.

PubMed

Michopoulos, Vasiliki

2016-11-01

The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

Stress-Induced Alterations in Estradiol Sensitivity Increase Risk for Obesity in Women

PubMed Central

Michopoulos, Vasiliki

2016-01-01

The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

Peptide YY: a potential therapy for obesity.

PubMed

Renshaw, D; Batterham, R L

2005-03-01

Obesity now represents a modern epidemic in western society with major health and economic consequences. Unfortunately, previous pharmacological approaches to the treatment of obesity have been associated with life-threatening side effects and limited efficacy. Over recent years there has been a marked increase in our understanding of the physiological mechanisms that regulate body weight and how these are perturbed in obesity. One therapeutic strategy is to develop drugs which both mimic and enhance the body's own satiety signals. The gut hormone peptide tyrosine tyrosine (PYY), which is released postprandially from the gastrointestinal tract, has recently been shown to be a physiological regulator of food intake. Peripheral administration of PYY reduces feeding in rodents via a mechanism which requires the Y2 receptor and is thought to primarily involve modulation of the hypothalamic arcuate nucleus (ARC) circuitry. In humans a single 90-minute infusion of PYY has been shown to markedly reduce subsequent 24-hour caloric intake in lean, normal-weight and obese subjects. Moreover, obese subjects have been found to have low levels of fasting and postprandial PYY suggesting a role for this hormone in the pathogenesis of obesity. Although studies examining the effects of chronic peripheral administration of PYY to humans are awaited, the results from continuous infusion studies in a number of obese rodent models are encouraging with reductions in food intake, body weight and adiposity observed. Potential therapeutic manipulations based on the PYY system include development of Y2 agonists, exogenously administration of PYY or increased endogenous release from the gastrointestinal tract.

Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis.

PubMed

Li, Li; Feng, Qiong; Ye, Ming; He, Yaojuan; Yao, Aling; Shi, Kun

2017-11-01

obesity. What are the implications of these findings for clinical practice and/or further research: Obesity, metabolic disorders and PCOS in adolescents are associated. Obesity exacerbates metabolic disorders in adolescent PCOS. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Therapeutic intervention combined with lifestyle modification may provide better treatment for adolescent PCOS. The aetiologies of PCOS combined with obesity in adolescents require further investigation.

Obesity Metaphors: How Beliefs about the Causes of Obesity Affect Support for Public Policy

PubMed Central

Barry, Colleen L; Brescoll, Victoria L; Brownell, Kelly D; Schlesinger, Mark

2009-01-01

Context: Relatively little is known about the factors shaping public attitudes toward obesity as a policy concern. This study examines whether individuals' beliefs about the causes of obesity affect their support for policies aimed at stemming obesity rates. This article identifies a unique role of metaphor-based beliefs, as distinct from conventional political attitudes, in explaining support for obesity policies. Methods: This article used the Yale Rudd Center Public Opinion on Obesity Survey, a nationally representative web sample surveyed from the Knowledge Networks panel in 2006/07 (N = 1,009). The study examines how respondents' demographic and health characteristics, political attitudes, and agreement with seven obesity metaphors affect support for sixteen policies to reduce obesity rates. Findings: Including obesity metaphors in regression models helps explain public support for policies to curb obesity beyond levels attributable solely to demographic, health, and political characteristics. The metaphors that people use to understand rising obesity rates are strong predictors of support for public policy, and their influence varies across different types of policy interventions. Conclusions: Over the last five years, the United States has begun to grapple with the implications of dramatically escalating rates of obesity. Individuals use metaphors to better understand increasing rates of obesity, and obesity metaphors are independent and powerful predictors of support for public policies to curb obesity. Metaphorical reasoning also offers a potential framework for using strategic issue framing to shift support for obesity policies. PMID:19298414

Obesity in the news: do photographic images of obese persons influence antifat attitudes?

PubMed

McClure, Kimberly J; Puhl, Rebecca M; Heuer, Chelsea A

2011-04-01

News coverage of obesity has increased dramatically in recent years, and research shows that media content may contribute to negative public attitudes toward obese people. However, no work has assessed whether photographic portrayals of obese people that accompany news stories affect attitudes. In the present study, the authors used a randomized experimental design to test whether viewing photographic portrayals of an obese person in a stereotypical or unflattering way (versus a nonstereotypical or flattering portrayal) could increase negative attitudes about obesity, even when the content of an accompanying news story is neutral. The authors randomly assigned 188 adult participants to read a neutral news story about the prevalence of obesity that was paired with 1 of 4 photographic portrayals of an obese adult (or no photograph). The authors subsequently assessed attitudes toward obese people using the Fat Phobia Scale. Participants in all conditions expressed a moderate level of fat phobia (M = 3.83, SD = 0.58). Results indicated that participants who viewed the negative photographs expressed more negative attitudes toward obese people than did those who viewed the positive photographs. Implications of these findings for the media are discussed, with emphasis on increasing awareness of weight bias in health communication and journalistic news reporting.

Psychedelics and hypnosis: Commonalities and therapeutic implications.

PubMed

Lemercier, Clément E; Terhune, Devin B

2018-06-01

Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention. Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy. We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes. Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.

Contraception and the obese woman

PubMed Central

Reifsnider, Elizabeth; Mendias, Nonie; Davila, Yolanda; Babendure, Jennie Bever

2016-01-01

Purpose Obesity has reached epidemic rates among U.S. women of reproductive age, many of whom want to use contraception. However, some forms of contraception can have adverse effects on an obese woman's health. This article explores risks of contraception available in the United States and provides clinical recommendations for use by obese women. Data sources Information was compiled by reviewing the scientific literature on contraception and female obesity using CINAHL, MEDLINE, PubMed search engines. Conclusions The evidence is largely supportive of combined oral contraceptive (COC) use in carefully screened obese women without known risks factors for cardiovascular disease. The efficacy of COCs may be slightly reduced in obese women because of increased body mass. Other types of hormonal contraceptives have varying safety and efficacy reports when used by obese women. Intrauterine devices do not have reduced efficacy nor increased risks for obese women but insertion may be more difficult. Obesity has no effect on efficacy of barrier methods of contraception. Implications Clinicians should conduct a careful history and physical exam with selected supporting laboratory tests when considering prescription of hormonal contraceptives for obese women. Obese women require health counseling to carefully follow directions for contraceptive use to avoid unintended pregnancy. PMID:24170564

Regarding Obesity as a Disease: Evolving Policies and Their Implications

PubMed Central

Dhurandhar, Emily J.; Allison, David B.

2016-01-01

Synopsis The 2013 decision of the American Medical Association (AMA) to recognize obesity as a complex, chronic disease that requires medical attention came as the result of developments over three decades. Defining a condition such as obesity to be a disease is a very public process that is largely driven by expectation of costs and benefits. Although the public has been slow to embrace defining obesity as a purely medical condition, evidence is emerging for broader awareness of factors beyond personal choice influencing obesity. The AMA decision appears to be working in concert with other factors to bring more access to care, less blame for people with the condition, and more favorable conditions for research to identify effective strategies for prevention and clinical care to reduce the impact of this disease. PMID:27519127

of obese Turkish female patients

PubMed

Özşahin, Akatlı Kürşad; Altıntaş, Ebru

2018-04-30

Background/aim: Mental disorders may accompany obesity. This study aims to evaluate the association between social anxiety disorder (SAD) and obesity and the risk factors for SAD in obese female patients. Materials and methods: A total of 114 obese patients and 110 healthy controls were included. The Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), State and Trait Anxiety Inventory (STAI I-II), and Liebowitz Social Anxiety Scale (LSAS) were administered to assess anxiety, depression, and social anxiety levels. Scale scores were analyzed statistically. Results: The rate of SAD in obese female patients was found to be 8.8%. Anxiety, depression, and social anxiety levels were significantly higher in the obesity group compared to the control group (P < 0.05). According to linear regression analyses, a significant association between LSAS anxiety level and age, prior surgery, social support, history of being teased, BDI, and BAI was found. Conclusion: The present study shows that many factors are related to obesity and SAD in obese female patients. The clinical implications of these findings should be considered. Interventions for these factors may help prevent SAD in obese female patients.

Fighting obesity: Non-pharmacological interventions.

PubMed

Higuera-Hernández, María Fernanda; Reyes-Cuapio, Elena; Gutiérrez-Mendoza, Marissa; Rocha, Nuno Barbosa; Veras, André Barciela; Budde, Henning; Jesse, Johanna; Zaldívar-Rae, Jaime; Blanco-Centurión, Carlos; Machado, Sérgio; Murillo-Rodríguez, Eric

2018-06-01

The abnormal or excessive fat accumulation that impairs health is one of the criteria that fulfills obesity. According to epidemiological data, obesity has become a worldwide public health problem that in turn would trigger additional pathologies such as cardiorespiratory dysfunctions, cancer, gastrointestinal disturbances, depression, sleep disorders, just to mention a few. Then, the search for a therapeutical intervention aimed to prevent and manage obesity has been the focus of study during the last years. As one can assume, the increased prevalence of obesity has translated to search of efficient pharmaceuticals designed to manage this health issue. However, to further complicate the scenario, scientific literature has described that obesity is the result of interaction between multiple events. Therefore, pharmacological approaches have faced a serious challenge for develop the adequate treatment. Here, we argue that a wide range of non-pharmacological/invasive techniques can be used to manage obesity, such as diets, cognitive behavioral interventions, exercise and transcranial direct current stimulation. Combining these techniques may allow improving quality of life of obese patients. Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Circadian rhythms and obesity in mammals.

PubMed

Froy, Oren

2012-01-01

Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding (RF), calorie restriction (CR), and intermittent fasting (IF), provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. This paper focuses on circadian rhythms and their link to obesity.

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

PubMed

Manna, Prasenjit; Jain, Sushil K

2015-12-01

Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

PubMed Central

Manna, Prasenjit

2015-01-01

Abstract Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue

The endocannabinoid system: a new pharmacological target for obesity treatment?

PubMed

Hu, Jia; Zhu, Chao; Huang, Mao

2009-06-01

Being a great threaten for human health, obesity has become a pandemic chronic disease. There have been several therapeutic treatments for this social health issue, including diet and exercise therapy, medication and surgery, among which the diet is still the most common way. However, none of these therapeutic measures available is ideal, making it necessary to find an effective medical treatment. The endocannabinoid system, which is well known for its contributions in certain mental processes such as relaxation, amelioration of pain and anxiety, and sedation initiation, has been recently reported to play an essential role in regulating appetite and metabolism to maintain energy balance, leading to the belief that endocannabinoid system is closely related to obesity. This new discovery deepens our understanding of obesity, and provides us with a new direction for clinical obesity treatment. Rimonabant is an antagonist for CB1, and has entered the market in some countries. However, although effective as an anti-obesity drug, rimonabant also causes obviously adverse side-effects, thus is being doubted and denied for medical usage.

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

PubMed Central

Ferro, Suellen; Azevedo-Silva, João; Casal, Margarida; Côrte-Real, Manuela; Baltazar, Fatima; Preto, Ana

2016-01-01

Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP). We provide evidence that acetate enters CRC cells by the secondary active transporters MCT1 and/or MCT2 and SMCT1 as well as by facilitated diffusion via aquaporins. CRC cell exposure to acetate upregulates the expression of MCT1, MCT4 and CD147, while promoting MCT1 plasma membrane localization. We also observed that acetate increases CRC cell glycolytic phenotype and that acetate-induced apoptosis and anti-proliferative effect was potentiated by 3BP. Our data suggest that acetate selectivity towards CRC cells might be explained by the fact that aquaporins and MCTs are found overexpressed in CRC clinical cases. Our work highlights the importance that acetate transport regulation has in the use of drugs such as 3BP as a new therapeutic strategy for CRC. PMID:28874966

The effect of the GLP‐1 analogue Exenatide on functional connectivity within an NTS‐based network in women with and without obesity

PubMed Central

Coveleskie, K.; Kilpatrick, L. A.; Gupta, A.; Stains, J.; Connolly, L.; Labus, J. S.; Sanmiguel, C.

2017-01-01

Summary Objective The differential effect of GLP‐1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite‐related behaviours was investigated in women with normal weight compared with women with obesity. Methods Following an 8‐h fast, 19 female subjects (11 lean, 8 obese) participated in a 2‐d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30‐min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug‐induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus. Results Women with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese. Conclusions Obesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP‐1 analogues in therapeutic interventions. PMID:29259802

Epigenetics and obesity.

PubMed

Campión, Javier; Milagro, Fermin; Martínez, J Alfredo

2010-01-01

The etiology of obesity is multifactorial, involving complex interactions among the genetic makeup, neuroendocrine status, fetal programming, and different unhealthy environmental factors, such as sedentarism or inadequate dietary habits. Among the different mechanisms causing obesity, epigenetics, defined as the study of heritable changes in gene expression that occur without a change in the DNA sequence, has emerged as a very important determinant. Experimental evidence concerning dietary factors influencing obesity development through epigenetic mechanisms has been described. Thus, identification of those individuals who present with changes in DNA methylation profiles, certain histone modifications, or other epigenetically related processes could help to predict their susceptibility to gain or lose weight. Indeed, research concerning epigenetic mechanisms affecting weight homeostasis may play a role in the prevention of excessive fat deposition, the prediction of the most appropriate weight reduction plan, and the implementation of newer therapeutic approaches. Copyright © 2010 Elsevier Inc. All rights reserved.

Implications of teen birth for overweight and obesity in adulthood.

PubMed

Chang, Tammy; Choi, HwaJung; Richardson, Caroline R; Davis, Matthew M

2013-08-01

The objective of this study was to examine whether teen birth was independently associated with overweight and obesity in a US cohort. We examined whether teen birth is independently associated with overweight and obesity in a multiyear US cohort using the 2001-2010 National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey of the US civilian, noninstitutionalized population. We performed multinomial logistic regression adjusting for survey cohort, age at survey, race, education, and parity. We included women 20-59 years old at the time of survey, with at least 1 live birth, not currently or recently pregnant (unweighted, n = 5220; weighted, n = 48.4 million). Our outcome measure was the effect of teen birth on subsequent overweight and obesity. In bivariate analyses, women with a teen birth were significantly more likely than women without a teen birth to be overweight (relative risk ratios [RRRs], 1.61; 95% confidence interval [CI], 1.37-1.90) or obese (RRR, 1.84; 95% CI, 1.56-2.16) at the time of the survey. In multivariate models, women with a teen birth remained significantly more likely to be overweight (adjusted RRR, 1.33; 95% CI, 1.10-1.62) or obese (adjusted RRR, 1.32; 95% CI, 1.09-1.61) than women without a teen birth. For women in the United States, giving birth as a teen is associated with subsequent overweight/obese status later in life. To inform clinical and policy interventions with the goal to improve the long-term health of teenage mothers, future studies must examine modifiable physiological and sociomedical reasons for early child-bearing and later risk of obesity. Copyright © 2013 Mosby, Inc. All rights reserved.

Comparison of ICD code-based diagnosis of obesity with measured obesity in children and the implications for health care cost estimates.

PubMed

Kuhle, Stefan; Kirk, Sara F L; Ohinmaa, Arto; Veugelers, Paul J

2011-12-21

Administrative health databases are a valuable research tool to assess health care utilization at the population level. However, their use in obesity research limited due to the lack of data on body weight. A potential workaround is to use the ICD code of obesity to identify obese individuals. The objective of the current study was to investigate the sensitivity and specificity of an ICD code-based diagnosis of obesity from administrative health data relative to the gold standard measured BMI. Linkage of a population-based survey with anthropometric measures in elementary school children in 2003 with longitudinal administrative health data (physician visits and hospital discharges 1992-2006) from the Canadian province of Nova Scotia. Measured obesity was defined based on the CDC cut-offs applied to the measured BMI. An ICD code-based diagnosis obesity was defined as one or more ICD-9 (278) or ICD-10 code (E66-E68) of obesity from a physician visit or a hospital stay. Sensitivity and specificity were calculated and health care cost estimates based on measured obesity and ICD-based obesity were compared. The sensitivity of an ICD code-based obesity diagnosis was 7.4% using ICD codes between 2002 and 2004. Those correctly identified had a higher BMI and had higher health care utilization and costs. An ICD diagnosis of obesity in Canadian administrative health data grossly underestimates the true prevalence of childhood obesity and overestimates the health care cost differential between obese and non-obese children.

Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity.

PubMed

Dudek, Magdalena; Marcinkowska, Monika; Bucki, Adam; Olczyk, Adrian; Kołaczkowski, Marcin

2015-12-01

5HT6 receptor antagonists offer the potential for safe and effective drugs against obesity, because they can reduce weight without causing serious side effects in the cardiovascular system. Also, their anorexic effect is associated with reduced food intake via an enhancement of satiety. In the present study we investigated the anorexic effect of idalopirdine (LuAE58054) in a model of obesity induced by high-fat diet. To induce obesity in rats, the animals were treated with feed with a fat content of 40 %. Body weight was controlled and the amount of food and water consumed was determined. The influence of the test compound on the lipid profile and glucose level was measured, as well as locomotor activity in home cages on the 20th day of the treatment. LuAE58054, at 5 mg kg(-1)/day i.p., was significantly anorectic in this model of obesity. Animals treated with LuAE58054 weighed 8 and 9.2 % less than the control obese animals on the 12th and 21st days, respectively. It significantly reduced food intake and the amount of peritoneal fat in animals, and reduced the level of triglycerides in plasma. LuAE58054 did not have a statistically significant effect on the spontaneous activity of diet-induced obese rats. The present study clearly demonstrates the effectiveness of LuAE58054 in reducing body weight. This compound is in phase III of clinical trials for the treatment of cognitive deficits associated with Alzheimer's disease and schizophrenia. It is a 5HT6 receptor antagonist and is, therefore, free of those unacceptable side effects that preclude chronic use of anti-obesity drugs with other mechanisms of action. The search for an effective and safe anti-obesity drug is essential for an increasingly obese population; therefore, the anorectic action of LuAE58054 is important and there is a need for more research in this direction.

Is Spinal Muscular Atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

PubMed Central

Simone, Chiara; Ramirez, Agnese; Bucchia, Monica; Rinchetti, Paola; Rideout, Hardy; Papadimitriou, Dimitra; Re, Diane B.; Corti, Stefania

2016-01-01

Spinal Muscular Atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the Survival Motor Neuron 1 (SMN1) gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. These contribution of non-motor neuronal cells to disease pathogenesis has important therapeutic implications: in fact, even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It will be crucial to take this evidence into account before clinical translation of the novel therapeutic approaches that are currently under development. PMID:26681261

Phosphodiesterase 4 inhibition as a potential new therapeutic target in obese women with polycystic ovary syndrome.

PubMed

Jensterle, Mojca; Kocjan, Tomaz; Janez, Andrej

2014-08-01

Phosphodiesterase (PDE) enzymes, including members of PDE4, have been investigated in the regulation of endocrine and reproductive functions of ovaries. In addition, selective inhibition of PDE4 enzyme has recently been implicated in the regulation of metabolism with positive effects on glucose homeostasis and weight reduction. The aim of this study was to evaluate whether the PDE4 inhibitor roflumilast affects body weight and hormonal and metabolic status in obese women with polycystic ovary syndrome (PCOS). Design/Participants/Main Outcome Measures: A 12-week prospective randomized open-label study was conducted with 36 obese women with PCOS diagnosed by the National Eunice Kennedy Shriver Institute of Child Health and Human Development criteria that had been pretreated with metformin (MET). They were randomized to MET 1000 mg twice a day or combined treatment (COM) with MET 1000 mg twice a day and roflumilast 500 μg every day. The primary outcome was change in anthropometric measures of obesity. Thirty-one patients (aged 33.8 ± 7.4 y, twice a day 36.4 ± 5.1 kg/m(2), mean ± SD) completed the study: 16 on MET and 15 on COM. Subjects treated with COM lost on average 4.2 ± 2.8 kg compared with a 0.9 ± 2.5 kg weight gain in the MET group (P = .025). Body mass index decreased for 1.6 ± 1.1 kg/m(2) in COM arm compared with increase for 0.9 ± 2.4 kg/m(2) in the MET arm (P = .046). Visceral adipose tissue area as assessed by dual-energy x-ray absorptiometry decreased from 136.7 ± 37.8 to 121.2 ± 36.2 cm(2) in the COM arm compared with an increase from 155.3 ± 61.9 to 166.7 ± 67.2 cm(2) in the MET arm (P = .02). From baseline to study end, both treatment interventions resulted in a significant reduction of androstenedione (P = .013), free T (P = .002), and homeostasis model assessment for insulin resistance score (P = .027) and a significant increase in SHBG (P = .024), although the between-treatment differences of the changes have not been statistically

Adenovirus 36 and Obesity: An Overview.

PubMed

Ponterio, Eleonora; Gnessi, Lucio

2015-07-08

There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed.

Adenovirus 36 and Obesity: An Overview

PubMed Central

Ponterio, Eleonora; Gnessi, Lucio

2015-01-01

There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed. PMID:26184280

Therapeutic Implications of a Barrier-Based Pathogenesis of Atopic Dermatitis

PubMed Central

Wakefield, Joan S.

2015-01-01

Excessive Th2 cell signaling and IgE production play key roles in the pathogenesis of atopic dermatitis (AD). Yet, recent information suggests that the inflammation in AD instead is initiated by inherited insults to the barrier, including a strong association between mutations in FILAGGRIN and SPINK5 in Netherton syndrome, the latter of which provides an important clue that AD is provoked by excess serine protease activity. But acquired stressors to the barrier may also be required to initiate inflammation in AD, and in addition, microbial colonization by Staphylococcus aureus both amplifies inflammation, but also further stresses the barrier in AD. Therapeutic implications of these insights are as follows: While current therapy has been largely directed toward ameliorating Th2-mediated inflammation and/or pruritus, these therapies are fraught with short-term and potential long-term risks. In contrast, “barrier repair” therapy, with a ceramide-dominant triple-lipid mixture of stratum corneum lipids, is more logical, of proven efficacy, and it provides a far-improved safety profile. PMID:21174234

Current and novel insights into the neurophysiology of migraine and its implications for therapeutics.

PubMed

Akerman, Simon; Romero-Reyes, Marcela; Holland, Philip R

2017-04-01

Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses. While there is still a clear lack of understanding of its neurophysiology, it is beginning to be understood, and it seems to suggest migraine is a disorder of brain sensory processing, characterized by a generalized neuronal hyperexcitability. The complex symptomatology of migraine indicates that multiple neuronal systems are involved, including brainstem and diencephalic systems, which function abnormally, resulting in premonitory symptoms, ultimately evolving to affect the dural trigeminovascular system, and the pain phase of migraine. The migraineur also seems to be particularly sensitive to fluctuations in homeostasis, such as sleep, feeding and stress, reflecting the abnormality of functioning in these brainstem and diencephalic systems. Implications for therapeutic development have grown out of our understanding of migraine neurophysiology, leading to major drug classes, such as triptans, calcitonin gene-related peptide receptor antagonists, and 5-HT 1F receptor agonists, as well as neuromodulatory approaches, with the promise of more to come. The present review will discuss the current understanding of the neurophysiology of migraine, particularly migraine headache, and novel insights into the complex neural networks responsible for associated neurological symptoms, and how interaction of these networks with migraine pain pathways has implications for the development of novel therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

[Trigeminal autonomic cephalgias: diagnostic and therapeutic implications].

PubMed

Rosenberg-Nordmann, Mirjam; Tölle, Thomas R; Sprenger, Till

2007-09-06

Trigeminal autonomic cephalgias (TACs) are primary headache syndromes characterized by severe short-lasting headaches accompanied by ipsilateral facial autonomic symptoms. The group includes cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting neuralgiform headache with conjunctival injection and tearing (SUNCT). By far, Cluster headache is the most frequent of these syndromes. Similar hypothalamic and trigeminovascular mechanisms have been discussed as pathophysiologic mechanisms for all TACs. The therapeutic strategies, however, differ considerably. Although unusual, structural lesions in TACs have been described, affecting the therapeutic management.

Public views on food addiction and obesity: implications for policy and treatment.

PubMed

Lee, Natalia M; Lucke, Jayne; Hall, Wayne D; Meurk, Carla; Boyle, Frances M; Carter, Adrian

2013-01-01

According to their advocates, neurobiological explanations of overeating, or "food addiction", have the potential to impact public understanding and treatment of obesity. In this study, we examine the public's acceptance of the concept of food addiction as an explanation of overeating and assess its effects upon their attitudes toward obese persons and the treatment of obesity. We conducted an online survey of 479 adults from the US (n = 215) and Australia (n = 264). There was substantial support for the idea of food addiction, particularly among obese participants. Over half favoured treating obesity as a type of addiction. Psychotherapy was believed to be the most effective treatment and educational and support programs were the preferred policies to address food addiction. There was very little support for increasing taxes on obesogenic foods. Despite the strong support for seeing obesity as a form of addiction, respondents still saw obesity as primarily the result of personal choices and emphasized the need for individuals to take responsibility for their eating. Our sample of the general public strongly supported the idea of obesity as a form of food addiction; but this did not translate into support of clinical and public health policies that experts believe are most likely to reduce the prevalence of obesity. The reasons for the apparent disjunction between support for food addiction and a strong emphasis on personal choice for weight warrant further examination.

Maraviroc modifies gut microbiota composition in a mouse model of obesity: a plausible therapeutic option to prevent metabolic disorders in HIV-infected patients.

PubMed

Pérez-Matute, Patricia; Pérez-Martínez, Laura; Aguilera-Lizarraga, Javier; Blanco, José R; Oteo, José A

2015-08-01

The proportion of HIV-infected patients with overweight/obesity has increased in recent years. These patients have an increased metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut microbiota composition arises as a promising tool to prevent the development of obesity and associated disorders. The aim of this study was to investigate the impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV-infected patients, on gut microbiota composition in a mouse model of obesity. Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b) MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus 300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days. Mice were euthanized after 16 weeks of treatment and cecal contents were removed to analyse by real-time PCR four bacterial orders from the most dominant phyla in gut. Mice fed with a HFD showed a significant increase in Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this order was positively associated with body weight gain, insulin resistance and fatty liver. HFD induced a significant decrease in Bacteroidales and Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on Clostridiales and Lactobacillales. MVC may constitute a new therapeutic option to prevent obesity and related disorders in HIV-infected patients.

Nonnutritive, Low Caloric Substitutes for Food Sugars: Clinical Implications for Addressing the Incidence of Dental Caries and Overweight/Obesity

PubMed Central

Roberts, Michael W.; Wright, J. Timothy

2012-01-01

Caries and obesity are two common conditions affecting children in the United States and other developed countries. Caries in the teeth of susceptible children have often been associated with frequent ingestion of fermentable sugars such as sucrose, fructose, glucose, and maltose. Increased calorie intake associated with sugars and carbohydrates, especially when associated with physical inactivity, has been implicated in childhood obesity. Fortunately, nonnutritive artificial alternatives and non-/low-caloric natural sugars have been developed as alternatives to fermentable sugars and have shown promise in partially addressing these health issues. Diet counseling is an important adjunct to oral health instruction. Although there are only five artificial sweeteners that have been approved as food additives by the Food and Drug Administration (FDA), there are additional five non-/low caloric sweeteners that have FDA GRAS (Generally Recognized as Safe) designation. Given the health impact of sugars and other carbohydrates, dental professionals should be aware of the nonnutritive non-/low caloric sweeteners available on the market and both their benefits and potential risks. Dental health professionals should also be proactive in helping identify patients at risk for obesity and provide counseling and referral when appropriate. PMID:22505906

Obesity-Induced Hypertension: Brain Signaling Pathways

PubMed Central

da Silva, Alexandre A.; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; de Lara Rodriguez, Cecilia E. P.; Hall, John E.

2017-01-01

Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review high-lights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension. PMID:27262997

Public Views on Food Addiction and Obesity: Implications for Policy and Treatment

PubMed Central

Lee, Natalia M.; Lucke, Jayne; Hall, Wayne D.; Meurk, Carla; Boyle, Frances M.; Carter, Adrian

2013-01-01

Background According to their advocates, neurobiological explanations of overeating, or “food addiction”, have the potential to impact public understanding and treatment of obesity. In this study, we examine the public’s acceptance of the concept of food addiction as an explanation of overeating and assess its effects upon their attitudes toward obese persons and the treatment of obesity. Methods and Findings We conducted an online survey of 479 adults from the US (n = 215) and Australia (n = 264). There was substantial support for the idea of food addiction, particularly among obese participants. Over half favoured treating obesity as a type of addiction. Psychotherapy was believed to be the most effective treatment and educational and support programs were the preferred policies to address food addiction. There was very little support for increasing taxes on obesogenic foods. Despite the strong support for seeing obesity as a form of addiction, respondents still saw obesity as primarily the result of personal choices and emphasized the need for individuals to take responsibility for their eating. Conclusions Our sample of the general public strongly supported the idea of obesity as a form of food addiction; but this did not translate into support of clinical and public health policies that experts believe are most likely to reduce the prevalence of obesity. The reasons for the apparent disjunction between support for food addiction and a strong emphasis on personal choice for weight warrant further examination. PMID:24086382

Obesity Increases Sensitivity to Endotoxin Liver Injury: Implications for the Pathogenesis of Steatohepatitis

NASA Astrophysics Data System (ADS)

Yang, Shi Qi; Zhi Lin, Hui; Lane, M. Daniel; Clemens, Mark; Diehl, Anna Mae

1997-03-01

Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive to endotoxin liver injury than males. LPS induction of tumor necrosis factor α (TNFα ), the proven affecter of endotoxin liver injury, is no greater in the livers, white adipose tissues, or sera of obese animals than in those of lean controls. Indeed, the lowest serum concentrations of TNF occur in female obese rodents, which exhibit the most endotoxin-induced liver injury. Several cytokines that modulate the biological activity of TNF are regulated abnormally in the livers of obese animals. After exposure to LPS, mRNA of interferon γ , which sensitizes hepatocytes to TNF toxicity, is overexpressed, and mRNA levels of interleukin 10, a TNF inhibitor, are decreased. The phagocytic activity of liver macrophages and the hepatic expression of a gene encoding a macrophage-specific receptor are also decreased in obesity. This new animal model of obesity-associated liver disease demonstrates that hepatic macrophage dysfunction occurs in obesity and suggests that this might promote steatohepatitis by sensitizing hepatocytes to endotoxin.

Gut microbiota and obesity.

PubMed

Gérard, Philippe

2016-01-01

The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

The wage effects of obesity: a longitudinal study.

PubMed

Baum, Charles L; Ford, William F

2004-09-01

We use National Longitudinal Survey of Youth (NLSY) data to examine the effects of obesity on wages by gender. Sample means indicate that both men and women experience a persistent obesity wage penalty over the first two decades of their careers. We then control for a standard set of socioeconomic and familial variables but find that standard covariates do not explain why obese workers experience persistent wage penalties. This suggests that other variables -- including job discrimination, health-related factors and/or obese workers' behavior patterns -- may be the channels through which obesity adversely affects wages. The study closes with a discussion of the public policy implications suggested by these findings.

Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics.

PubMed

Wu, Yuan Seng; Lee, Zhong Yang; Chuah, Lay-Hong; Mai, Chun Wai; Ngai, Siew Ching

2018-04-30

Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC is discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

PubMed Central

Cai, HuaLin; Cao, Ting; Zhou, Xiang; Yao, Jeffrey K.

2018-01-01

Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents. PMID:29568275

Antimicrobial Dose in Obese Patient

PubMed Central

Kassab, Sawsan; Syed Sulaiman, Syed Azhar; Abdul Aziz, Noorizan

2007-01-01

Introduction Obesity is a chronic disease that has become one of major public health issue in Malaysia because of its association with other disease states including cardiovascular disease and diabetes. Despite continuous efforts to educate the public about the health risks associated with obesity, prevalence of the disease continues to increase. Dosing of many medications are based on weight, limited data are available on how antimicrobial agents should be dosed in obesity. The aim of this case presentation is to discuss dose of antibiotic in obese patient. Case report: Patient: GMN, Malay, Female, 45 year old, 150kg, transferred from medical ward to ICU with problems of fever, orthopnea, sepsis secondary to nosocomial pneumonia. She was admitted to hospital a week ago for SOB on exertion, cyanosis, mildly dyspneic, somasthenia, bilateral ankle swelling. There was no fever, cough, chest pain, clubbing, flapping tremor. Her grand father has pre-morbid history of obesity, HPT, DM and asthma. She was non alcoholic, smoker, and not on diet control. The diagnosis Pickwickian syndrome was made. Patient was treated with IV Dopamine 11mcg/kg/min, IV Morphine 4mg/h. IV GTN 15mcg/min, IV Ca gluconate 10g/24h for 3/7, IV Zantac 50mg tds, IV Augmentin 1.2g tds, IV Lasix 40mg od, IV Plasil 10mg tds, S.c heparin 5000IU bd. patient become stable and moved to medical ward to continue her treatment. Discussion: The altered physiologic function seen in obese patients is a concern in patients receiving antimicrobial agents because therapeutic outcomes depend on achieving a minimum inhibitory concentration (MIC). The therapeutic effect of any drug can be altered when any of the 4 pharmacokinetic processes (absorption, distribution, metabolism, or elimination) are altered. Decreased blood flow rates and increased renal clearance in obese patients can affect drug distribution and elimination. Changes in serum protein levels can change the metabolism and distribution of drugs that are

Recent advancements in drug treatment of obesity.

PubMed

Carter, Rebeca; Mouralidarane, Angelina; Ray, Shuvra; Soeda, Junpei; Oben, Jude

2012-10-01

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

PubMed Central

Anandhakrishnan, Ananthi; Korbonits, Márta

2016-01-01

Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose (3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed anti-obesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and long-term weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need. PMID:28031776

Gut Microbiota and Energy Expenditure in Health and Obesity.

PubMed

Bakker, Guido J; Zhao, Jing; Herrema, Hilde; Nieuwdorp, Max

2015-01-01

The contribution of intestinal bacterial strains (gut microbiota) to the development of obesity and obesity-related disorders is increasingly recognized as a potential diagnostic and pharmacologic target. Alterations in the intestinal bacterial composition have been associated with presence of chronic low-grade inflammation, a known feature of insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. Fecal transplantation studies in germ-free mice have provided crucial insight into the causality of gut microbiota in development of obesity and obesity-related disorders. Moreover, fecal transplantation studies in conjunction with fecal sampling in prospectively followed cohorts will help identify causally involved intestinal bacterial strains in human obesity. Results from these studies will lead to characterization of novel diagnostic markers as well as therapeutic strategies that aim to treat obesity and obesity-related disorders.

[Inflammation and obesity (lipoinflammation)].

PubMed

Izaola, Olatz; de Luis, Daniel; Sajoux, Ignacio; Domingo, Joan Carles; Vidal, Montse

2015-06-01

Obesity is a chronic disease with multiple origins. It is a widespread global phenomenon carrying potentially serious complications which requires a multidisciplinary approach due to the significant clinical repercussions and elevated health costs associated with the disease. The most recent evidence indicates that it shares a common characteristic with other prevalent, difficult-to-treat pathologies: chronic, low-grade inflammation which perpetuates the disease and is associated with multiple complications. The current interest in lipoinflammation or chronic inflammation associated with obesity derives from an understanding of the alterations and remodelling that occurs in the adipose tissue, with the participation of multiple factors and elements throughout the process. Recent research highlights the importance of some of these molecules, called pro-resolving mediators, as possible therapeutic targets in the treatment of obesity. This article reviews the evidence published on the mechanisms that regulate the adipose tissue remodelling process and lipoinflammation both in obesity and in the mediators that are directly involved in the appearance and resolution of the inflammatory process. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Canine obesity: an overview.

PubMed

Gossellin, J; Wren, J A; Sunderland, S J

2007-08-01

Canine patients are generally regarded as being clinically obese when their body weight is at least 15% above ideal. The incidence of obesity in dogs is thought to be in the range of 20-40% of the general population and, since obesity is known to predispose or exacerbate a range of serious medical conditions, its importance cannot be overstated. Management of obesity through dietary restriction and increased exercise is often difficult to achieve and dependent upon owner compliance. Until recently there has been no authorized therapeutic medication available for weight reduction in dogs, and drugs used in people have proved unsuitable. However, with the development of microsomal triglyceride transfer protein inhibitors for canine use, such as dirlotapide, the veterinarian has a novel method with which to augment traditional weight control programmes. This approach has the additional advantage that weight loss is achieved without dietary restriction or change in exercise regimen, providing encouragement for the owner to comply with subsequent dietary and exercise recommendations, thereby increasing the likelihood for long-term success.

Therapeutic potential of fecal microbiota transplantation.

PubMed

Smits, Loek P; Bouter, Kristien E C; de Vos, Willem M; Borody, Thomas J; Nieuwdorp, Max

2013-11-01

There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal conditions that were not previously considered to be associated with the intestinal microbiota. Although it is not clear if changes in the microbiota cause these conditions, we review the most current and best methods for performing fecal microbiota transplantation and summarize clinical observations that have implicated the intestinal microbiota in various diseases. We also discuss case reports of fecal microbiota transplantations for different disorders, including Clostridium difficile infection, irritable bowel syndrome, inflammatory bowel diseases, insulin resistance, multiple sclerosis, and idiopathic thrombocytopenic purpura. There has been increasing focus on the interaction between the intestinal microbiome, obesity, and cardiometabolic diseases, and we explore these relationships and the potential roles of different microbial strains. We might someday be able to mine for intestinal bacterial strains that can be used in the diagnosis or treatment of these diseases. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Microbiota and Obesity.

PubMed

Isolauri, Erika

2017-01-01

Obesity is globally the most prevalent nutritional disorder. Multifaceted therapeutic approaches are called for to halt the cascade from neonatal adiposity/high birth weight to childhood excessive weight gain/adult obesity with comorbidities. Recent experimental and clinical data provide one new target for interventions aiming to close this vicious circle: the microbiota. An aberrant gut microbiota, dysbiosis, induces immune and metabolic disturbances both locally and, consequent upon impaired gut barrier function, also systemic low-grade inflammation, which is causally linked to insulin resistance. The gut microecology could thus fill the gap between energy intake and expenditure by processing nutrients and regulating their access to and storage in the body, producing chemicals of hormonal nature and controlling the secretion of proinflammatory mediators locally and systemically. Conversely, being highly sensitive to environmental impacts, particularly to early feeding, the compositional development of the gut microbiota may prove the target of choice in efforts to reduce the risk of obesity. It has been demonstrated that a lower number of bifidobacteria precedes the development of obesity, and a dearth of butyrate-producing bacteria and an overall richness of bacteria increase the risk of metabolic disease; moreover, recognition that practices known to disrupt the early gut microbiota, e.g., cesarean section delivery and antibiotic exposure, contribute to obesity, encourages to pursue this line of research. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

PubMed

Hecker, Louise

2018-04-01

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

Role of MicroRNA Regulation in Obesity-Associated Breast Cancer: Nutritional Perspectives.

PubMed

Kasiappan, Ravi; Rajarajan, Dheeran

2017-11-01

Breast cancer is the most common malignancy diagnosed in women, and the incidence of breast cancer is increasing every year. Obesity has been identified as one of the major risk factors for breast cancer progression. The mechanisms by which obesity contributes to breast cancer development is not yet understood; however, there are a few mechanisms counted as potential producers of breast cancer in obesity, including insulin resistance, chronic inflammation and inflammatory cytokines, adipokines, and sex hormones. Recent emerging evidence suggests that alterations in microRNA (miRNA) expressions are found in several diseases, including breast cancer and obesity; however, miRNA roles in obesity-linked breast cancer are beginning to unravel. miRNAs are thought to be potential noninvasive biomarkers for diagnosis and prognosis of cancer patients with comorbid conditions of obesity as well as therapeutic targets. Recent studies have evidenced that nutrients and other dietary factors protect against cancer and obesity through modulation of miRNA expressions. Herein, we summarize a comprehensive overview of up-to-date information related to miRNAs and their molecular targets involved in obesity-associated breast cancer. We also address the mechanisms by which dietary factors modulate miRNA expression and its protective roles in obesity-associated breast cancer. It is hoped that this review would provide new therapeutic strategies for the treatment of obesity-associated breast cancer to reduce the burden of breast cancer. © 2017 American Society for Nutrition.

Pharmacotherapy in the Management of Pediatric Obesity.

PubMed

Kelly, Aaron S; Fox, Claudia K

2017-08-01

This review provides a rationale for the use of pharmacotherapy in pediatric weight management, summarizes results of some of the key pediatric clinical trials of approved and "off-label" obesity medications, introduces new options in the pediatric pipeline, and offers a glimpse into the future of pediatric obesity medicine. Despite the need for adjunctive treatments to enhance the outcomes of lifestyle modification therapy among youth with obesity, none of the obesity medications evaluated to date have been shown to meaningfully reduce BMI or cardiometabolic risk factors. Promising medications recently approved for the treatment of obesity in adults will soon be tested in pediatric trials, offering hope that new therapeutic options will soon be available. As new medications are approved to treat pediatric obesity, it will be important to evaluate the safety and efficacy of combination pharmacotherapy and investigate predictors of response. Application of precision medicine approaches to the field of pediatric obesity management will improve the long-term outlook for the tens of millions of youth afflicted with this serious and recalcitrant disease.

Cytotoxic and Cytolytic Cnidarian Venoms. A Review on Health Implications and Possible Therapeutic Applications

PubMed Central

Mariottini, Gian Luigi; Pane, Luigi

2013-01-01

The toxicity of Cnidaria is a subject of concern for its influence on human activities and public health. During the last decades, the mechanisms of cell injury caused by cnidarian venoms have been studied utilizing extracts from several Cnidaria that have been tested in order to evaluate some fundamental parameters, such as the activity on cell survival, functioning and metabolism, and to improve the knowledge about the mechanisms of action of these compounds. In agreement with the modern tendency aimed to avoid the utilization of living animals in the experiments and to substitute them with in vitro systems, established cell lines or primary cultures have been employed to test cnidarian extracts or derivatives. Several cnidarian venoms have been found to have cytotoxic properties and have been also shown to cause hemolytic effects. Some studied substances have been shown to affect tumour cells and microorganisms, so making cnidarian extracts particularly interesting for their possible therapeutic employment. The review aims to emphasize the up-to-date knowledge about this subject taking in consideration the importance of such venoms in human pathology, the health implications and the possible therapeutic application of these natural compounds. PMID:24379089

Cytotoxic and cytolytic cnidarian venoms. A review on health implications and possible therapeutic applications.

PubMed

Mariottini, Gian Luigi; Pane, Luigi

2013-12-27

The toxicity of Cnidaria is a subject of concern for its influence on human activities and public health. During the last decades, the mechanisms of cell injury caused by cnidarian venoms have been studied utilizing extracts from several Cnidaria that have been tested in order to evaluate some fundamental parameters, such as the activity on cell survival, functioning and metabolism, and to improve the knowledge about the mechanisms of action of these compounds. In agreement with the modern tendency aimed to avoid the utilization of living animals in the experiments and to substitute them with in vitro systems, established cell lines or primary cultures have been employed to test cnidarian extracts or derivatives. Several cnidarian venoms have been found to have cytotoxic properties and have been also shown to cause hemolytic effects. Some studied substances have been shown to affect tumour cells and microorganisms, so making cnidarian extracts particularly interesting for their possible therapeutic employment. The review aims to emphasize the up-to-date knowledge about this subject taking in consideration the importance of such venoms in human pathology, the health implications and the possible therapeutic application of these natural compounds.

Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.

PubMed

Han, Wei; Li, Jun; Tang, Huaping; Sun, Lixin

2017-03-04

Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level. Copyright © 2017 Elsevier Inc. All rights reserved.

Gynaecological issues affecting the obese adolescent.

PubMed

Wood, Paul L; Bauman, Dvora

2015-05-01

The implications of obesity in childhood and adolescence resonate into adulthood and have implications at different levels that include psychosocial and health issues that impact beyond reproductive performance. This chapter explores the various facets and consequences on gynaecological issues of increased Body Mass Index in childhood, including the link with puberty, pubertal menorrhagia (also affecting children with complex needs) and the all too common problems surrounding hyperandrogenism, insulin resistance and the polycystic ovarian syndrome in particular which need to be seen in the specific context of the adolescent years. The wider ramifications of obesity on the psychosocial welfare of adolescents merits special attention. Finally management strategies are considered in the context of the needs of adolescents. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Pharmacological inhibition of protein tyrosine phosphatase 1B: a promising strategy for the treatment of obesity and type 2 diabetes mellitus.

PubMed

Panzhinskiy, E; Ren, J; Nair, S

2013-01-01

Obesity and metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide. Obesity is the leading risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and non-alcoholic fatty liver disease. Obesity-associated insulin resistance, which is characterized by reduced uptake and utilization of glucose in muscle, adipose and liver tissues, is a key predictor of metabolic syndrome and T2DM. With increasing prevalence of obesity in adults and children, the need to identify and characterize potential targets for treating metabolic syndrome is imminent. Emerging evidence from animal models, clinical studies and cell lines studies suggest that protein tyrosine phosphatase 1B (PTP1B), an enzyme that negatively regulates insulin signaling, is likely to be involved in the pathways leading to insulin resistance. PTP1B is tethered to the cytosolic surface of endoplasmic reticulum (ER), an organelle that is responsible for folding, modification, and trafficking of proteins. Recent evidence links the disruption of ER homeostasis, referred to as ER stress, to the pathogenesis of obesity and T2DM. PTP1B has been recognized as an important player linking ER stress and insulin resistance in obese subjects. This review highlights recent advances in the research related to the role of PTP1B in signal transduction processes implicated in pathophysiology of obesity and type 2 diabetes, and focuses on the potential therapeutic exploitation of PTP1B inhibitors for the management of these conditions.

Therapeutic effects of metformin and clomiphene in combination with lifestyle intervention on infertility in women with obese polycystic ovary syndrome.

PubMed

Zhang, Jing; Si, Qinqin; Li, Jinqiong

2017-01-01

To evaluate the therapeutic effects of metformin and clomiphene in combination with lifestyle adjustment on infertility in women with obese polycystic ovarian syndrome (PCOS). A total of 101 infertile women with obese PCOS admitted to our hospital from July 2013 to July 2015 were randomly divided into an observation group (n=51) and a control group (n=50). The control group was treated with metformin plus clomiphene, based on which the observation group was also subjected to lifestyle adjustment. The body weight, body mass index (BMI) and waist-to-hip ratio (WHR) were measured before and after treatment. The changes of reproductive hormones, ovaries and endometrium were detected, and the rates of menstrual recovery, ovulation and pregnancy were observed. The body weight and BMI of the observation group after treatment were significantly lower than those before treatment and of the control group (P<0.05). There was no significant difference in WHR between the two groups. In the observation group, there were significant differences in LH, T, LH/FSH, FINS and TG levels before and after treatment and from those of the control group after treatment (P<0.05). Both the left and right ovarian volumes of the observation group after treatment were significantly lower than those before treatment and of the control group after treatment (P<0.05). The menstrual recovery, ovulation and pregnancy rates of the observation group were significantly higher than those of the control group (P<0.05). Lifestyle adjustment combined with metformin and clomiphene can improve the reproductive endocrine and lipid metabolism of obese PCOS patients, decrease the volumes of left and right ovaries, and increase the menstrual recovery, ovulation and pregnancy rates.

[Pharmacotherapy of obesity].

PubMed

Rotthoff, Thomas; Scherbaum, Werner A

2006-12-01

Long-term success in obesity therapy is difficult to obtain, therefore drug therapy appears to be helpful. Until today, end-point studies for obesity drugs beyond the improvement of individual surrogate parameters are still missing. For all available drugs, medical treatment can be recommended only for a limited period of time due to the data of the studies and under consideration of side effects. Although a weight reduction leads to an improvement of cardiovascular risk factors and hence a reduction of cardiovascular morbidity and mortality should be expected, no study could prove it so far. Despite the positive influence on individual surrogate parameters, the use of the present available therapies appears underwhelming. In this overview the approved substances and perspectives of new therapeutic concepts are represented.

Obesity Reduces Cognitive and Motor Functions across the Lifespan

PubMed Central

Wang, Chuanming; Chan, John S. Y.; Ren, Lijie; Yan, Jin H.

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. PMID:26881095

Obesity Reduces Cognitive and Motor Functions across the Lifespan.

PubMed

Wang, Chuanming; Chan, John S Y; Ren, Lijie; Yan, Jin H

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised.

JNK Activation of BIM Promotes Hepatic Oxidative Stress, Steatosis, and Insulin Resistance in Obesity.

PubMed

Litwak, Sara A; Pang, Lokman; Galic, Sandra; Igoillo-Esteve, Mariana; Stanley, William J; Turatsinze, Jean-Valery; Loh, Kim; Thomas, Helen E; Sharma, Arpeeta; Trepo, Eric; Moreno, Christophe; Gough, Daniel J; Eizirik, Decio L; de Haan, Judy B; Gurzov, Esteban N

2017-12-01

The members of the BCL-2 family are crucial regulators of the mitochondrial pathway of apoptosis in normal physiology and disease. Besides their role in cell death, BCL-2 proteins have been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism. It remains unclear, however, whether these proteins have a physiological role in glucose homeostasis and metabolism in vivo. In this study, we report that fat accumulation in the liver increases c-Jun N-terminal kinase-dependent BCL-2 interacting mediator of cell death (BIM) expression in hepatocytes. To determine the consequences of hepatic BIM deficiency in diet-induced obesity, we generated liver-specific BIM-knockout (BLKO) mice. BLKO mice had lower hepatic lipid content, increased insulin signaling, and improved global glucose metabolism. Consistent with these findings, lipogenic and lipid uptake genes were downregulated and lipid oxidation enhanced in obese BLKO mice. Mechanistically, BIM deficiency improved mitochondrial function and decreased oxidative stress and oxidation of protein tyrosine phosphatases, and ameliorated activation of peroxisome proliferator-activated receptor γ/sterol regulatory element-binding protein 1/CD36 in hepatocytes from high fat-fed mice. Importantly, short-term knockdown of BIM rescued obese mice from insulin resistance, evidenced by reduced fat accumulation and improved insulin sensitivity. Our data indicate that BIM is an important regulator of liver dysfunction in obesity and a novel therapeutic target for restoring hepatocyte function. © 2017 by the American Diabetes Association.

Obesity Prevention and Weight Maintenance After Loss.

PubMed

German, Alexander James

2016-09-01

Obesity is one of the most prevalent medical diseases in pets. Outcomes are often disappointing; many animals either fail to reach target weight or regain weight. This article discusses managing obesity, focusing on prevention. It gives guidance on establishing monitoring programs that use regular body weight and condition assessments to identify animals at risk of inappropriate weight gain, enabling early intervention. Weight management in obese animals is a lifelong process. Regular weight and body condition monitoring are key to identifying animals that rebound early, while continuing to feed a therapeutic weight loss diet can help prevent it from happening. Copyright © 2016 Elsevier Inc. All rights reserved.

Fighting obesity or obese persons? Public perceptions of obesity-related health messages.

PubMed

Puhl, R; Peterson, J L; Luedicke, J

2013-06-01

This study examined public perceptions of obesity-related public health media campaigns with specific emphasis on the extent to which campaign messages are perceived to be motivating or stigmatizing. In summer 2011, data were collected online from a nationally representative sample of 1014 adults. Participants viewed a random selection of 10 (from a total of 30) messages from major obesity public health campaigns from the United States, the United Kingdom and Australia, and rated each campaign message according to positive and negative descriptors, including whether it was stigmatizing or motivating. Participants also reported their familiarity with each message and their intentions to comply with the message content. Participants responded most favorably to messages involving themes of increased fruit and vegetable consumption, and general messages involving multiple health behaviors. Messages that have been publicly criticized for their stigmatizing content received the most negative ratings and the lowest intentions to comply with message content. Furthermore, messages that were perceived to be most positive and motivating made no mention of the word 'obesity' at all, and instead focused on making healthy behavioral changes without reference to body weight. These findings have important implications for framing messages in public health campaigns to address obesity, and suggest that certain types of messages may lead to increased motivation for behavior change among the public, whereas others may be perceived as stigmatizing and instill less motivation to improve health.

Maternal immigrant status and high birth weight: implications for childhood obesity.

PubMed

El-Sayed, Abdulrahman M; Galea, Sandro

2011-01-01

Childhood obesity, a growing epidemic, is associated with greater risk of several chronic diseases in adulthood. Children of immigrant mothers are at higher risk for obesity than children of non-immigrant mothers. High birth weight is the most important neonatal predictor of childhood obesity in the general population. To understand the etiology of obesity in children of immigrant mothers, we assessed the relation between maternal immigrant status and risk for high birth weight. Data about all births in Michigan (N = 786,868) between 2000-2005 were collected. We used bivariate chi-square tests and multivariate logistic regression models to assess the relation between maternal immigrant status and risk for neonatal high birth weight. The prevalence of high birth weight among non-immigrant mothers was 10.6%; the prevalence among immigrant mothers was 8.0% (P < .01). In multivariate regression models adjusted for maternal age, education, marital status, parity, and tobacco use, children of immigrant mothers had lower odds (odds ratio = 0.69, 95% confidence interval = 0.67-0.70) of high birth weight compared to those of non-immigrant mothers. Although maternal immigrant status has been shown to be associated with greater childhood obesity, surprisingly, children of immigrant mothers have lower risk of high birth weight than children of non-immigrant mothers. This suggests that factors in early childhood, potentially cultural or behavioral factors, may play a disproportionately important role in the etiology of childhood obesity in children of immigrant vs non-immigrant mothers.

Oxidative and inflammatory signals in obesity-associated vascular abnormalities.

PubMed

Reho, John J; Rahmouni, Kamal

2017-07-15

Obesity is associated with increased cardiovascular morbidity and mortality in part due to vascular abnormalities such as endothelial dysfunction and arterial stiffening. The hypertension and other health complications that arise from these vascular defects increase the risk of heart diseases and stroke. Prooxidant and proinflammatory signaling pathways as well as adipocyte-derived factors have emerged as critical mediators of obesity-associated vascular abnormalities. Designing treatments aimed specifically at improving the vascular dysfunction caused by obesity may provide an effective therapeutic approach to prevent the cardiovascular sequelae associated with excessive adiposity. In this review, we discuss the recent evidence supporting the role of oxidative stress and cytokines and inflammatory signals within the vasculature as well as the impact of the surrounding perivascular adipose tissue (PVAT) on the regulation of vascular function and arterial stiffening in obesity. In particular, we focus on the highly plastic nature of the vasculature in response to altered oxidant and inflammatory signaling and highlight how weight management can be an effective therapeutic approach to reduce the oxidative stress and inflammatory signaling and improve vascular function. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Issues in formulary management: therapeutic interchange. The value, cost, and quality of therapeutic interchange.

PubMed

Mahoney, C D

1992-10-01

Therapeutic interchange is a process of substituting a prescribed medication with one that offers therapeutic and cost benefits. The practice not only provides short-term savings but also is associated with decreases in lengths of stay in hospitals and total hospital drug expenses. There may be medicolegal implications when FDA-approved indications differ for interchanged drugs. The potential for liability is decreased when a standard of care is met, but since standards can change, guidelines should be reviewed regularly. High-tech, high-cost drugs are sometimes appropriate for therapeutic interchange. Pharmacy and therapeutics committees should assure best value by considering indirect expenses, quality, and therapeutic outcome, as well as product cost. Therapeutic interchange programs enable pharmacy managers to neutralize or at least slow the rate of drug cost increases, ensuring appropriate utilization of resources and more favorable patient outcomes.

Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes.

PubMed

Yong, Seok-Beom; Song, Yoonsung; Kim, Yong-Hee

2017-12-01

Obesity is an increasingly prevalent global health problem. Due to its close relations with metabolic diseases and cancer, new therapeutic approaches for treating obesity and obesity-induced metabolic diseases are required. Visceral white adipose tissue (WAT) has been closely associated with obesity-induced inflammation and adipose tissue macrophages (ATMs) are responsible for obesity-induced inflammation by releasing inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6. TNF-α converting enzyme (TACE) is a transmembrane enzyme that induces the enzymatic cleavage and release of inflammatory cytokines. In this study, we developed a nonviral gene delivery system consisting of an oligopeptide (ATS-9R) that can selectively target visceral ATMs. In here we shows visceral adipose tissue-dominant inflammatory gene over-expressions in obese mouse and our strategy enabled the preferential delivery of therapeutic genes to visceral ATMs and successfully achieved ATM-targeted gene silencing. Finally, ATS-9R-mediated TACE gene silencing in visceral ATMs alleviated visceral fat inflammation and improved type 2 diabetes by reducing whole body inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perioperative Care of the Obese Cardiac Surgical Patient.

PubMed

Chacon, M Megan; Cheruku, Sreekanth R; Neuburger, Peter J; Lester, Laeben; Shillcutt, Sasha K

2017-12-13

Morbid obesity is associated with impairment of cardiovascular, pulmonary, gastrointestinal, and renal physiology with significant perioperative consequences and has been linked with higher morbidity and mortality after cardiac surgery. Cardiac surgery patients have a higher incidence of difficult airway and difficult laryngoscopy than general surgery patients do, and obesity is associated with difficult mask ventilation and direct laryngoscopy. Positioning injuries occur more frequently because obese patients are at greater risk of pressure injury, such as rhabdomyolysis and compartment syndrome. Despite the association between obesity and several chronic disease states, the effects of obesity on perioperative outcomes are conflicting. Studies examining outcomes of overweight and obese patients in cardiac surgery have reported varying results. An "obesity paradox" has been described, in which the mortality for overweight and obese patients is lower compared with patients of normal weight. This review describes the physiologic abnormalities and clinical implications of obesity in cardiac surgery and summarizes recommendations for anesthesiologists to optimize perioperative care of the obese cardiac surgical patient. Copyright © 2017 Elsevier Inc. All rights reserved.

[Food addiction: Definition, measurement and limits of the concept, associated factors, therapeutic and clinical implications].

PubMed

Cathelain, Sarah; Brunault, Paul; Ballon, Nicolas; Réveillère, Christian; Courtois, Robert

2016-12-01

Addictions, which are characterized by the inability to control a behavior despite existence of physical or psychological consequences, have biological, psychological and social determinants. Although the possibility of developing an addiction to some psychoactive substances (e.g. alcohol, tobacco, cannabis) and to gambling (i.e., gambling disorder) is now well demonstrated, the possibility to develop a non-drug addiction (i.e., behavioral addiction) to certain behaviors which provide pleasure (e.g. eating, having sex, buying things) is still in debate. The concept of food addiction, which refers to people who exhibit substance dependence criteria in relation to some high-fat and high-sugar foods, was recently proposed by applying substance dependence DSM criteria to eating behavior. To assess food addiction, the Yale Food Addiction Scale is now the only self-administered questionnaire (diagnosis and estimate of the number of symptoms of food addiction). Prevalence for food addiction is higher in overweight and obese patients, and in patients with certain psychopathological characteristics (i.e., depression, Attention Deficit Hyperactivity Disorder, high impulsivity), in patients who are single and in patients with neurobiological alterations in the reward system. However, it is still unclear whether food addiction is necessary associated with subsequent increase in body weight and/or obesity. An increasing number of studies demonstrated that drug addiction and food addiction shares some similar clinical, neurobiological and psychopathological and sociocultural risk factors. To test the pertinence to include food addiction as an addiction, it would be interesting to conduct future studies in patients who may experience harms related to their food addiction, including not only patients with obesity, but also patients with metabolic syndrome, type 2 diabetes, hypertension, dyslipidemia, atherosclerosis, stroke, or coronary heart disease. Food addiction is a clinical

Hypothalamic inflammation and gliosis in obesity

PubMed Central

Dorfman, Mauricio D.; Thaler, Joshua P.

2015-01-01

Structured Abstract Purpose of review Hypothalamic inflammation and gliosis are recently discovered mechanisms that may contribute to obesity pathogenesis. Current research in this area suggests that investigation of these CNS responses may provide opportunities to develop new weight loss treatments. Recent findings In rodents, hypothalamic inflammation and gliosis occur rapidly with high-fat diet consumption prior to significant weight gain. In addition, sensitivity or resistance to diet-induced obesity in rodents generally correlates with the presence or absence of hypothalamic inflammation and reactive gliosis (brain response to injury). Moreover, functional interventions that increase or decrease inflammation in neurons and glia correspondingly alter diet-associated weight gain. However, some conflicting data have recently emerged that question the contribution of hypothalamic inflammation to obesity pathogenesis. However, several studies have detected gliosis and disrupted connectivity in obese humans, highlighting the potential translational importance of this mechanism. Summary There is growing evidence that obesity is associated with brain inflammation in humans, particularly in the hypothalamus where its presence may disrupt body weight control and glucose homeostasis. More work is needed to determine whether this response is common in human obesity and to what extent it can be manipulated for therapeutic benefit. PMID:26192704

Effects of zinc supplementation on obesity: study protocol for a randomized controlled clinical trial.

PubMed

Rathnayake, Kumari M; Silva, Kdrr; Jayawardena, Ranil

2016-11-04

The prevalence of obesity is escalating alarmingly worldwide, and it is now becoming a rapidly growing epidemic in developing countries. Recent studies have reported that zinc has been implicated in altered lipid markers, insulin resistance and some obesity markers. There is a lack of evidence on zinc as a potential therapeutic agent to reduce weight and improve metabolic parameters in obese adults. The present study is designed to evaluate the effects of zinc supplementation on obese adults in Sri Lanka. Furthermore, we aim to evaluate the effects of zinc supplementation on metabolic parameters in this population. This study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 3 months at the clinical laboratory, Department of Applied Nutrition, Wayamba University of Sri Lanka to assess the efficacy of daily zinc 20 mg supplementation in obese subjects. There will be a total of 80 subjects, aged between 18-60 years, of both genders, who are obese (body mass index (BMI) ≥25). Subjects will be stratified according to age, gender and BMI and randomly assigned into the test and placebo groups in a 1:1 ratio. The treatment drug is a capsule containing elemental zinc 20 mg as the active ingredient (as zinc sulphate). The placebo capsule will contain lactose monohydrate. The subjects will receive either zinc capsules or placebo daily for 3 months. The study treatments will be double blinded to both investigator and subject. The visits and the evaluations will be as follows: screening (visit 0), baseline (visit 1) and 3 month (visit 2). The primary outcome will be weight reduction among the obese subjects. Secondary outcome measures include glycaemic status (fasting blood glucose), lipid parameters (total cholesterol, triglyceride levels, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) and blood pressure. The trial protocol will aim to establish the effects of zinc supplementation on weight

Role of inflammation in obesity-related breast cancer.

PubMed

Crespi, Elisa; Bottai, Giulia; Santarpia, Libero

2016-12-01

Chronic inflammation associated with obesity is now recognized to be an important condition in promoting carcinogenesis and progression in breast cancer patients, mostly in postmenopausal women with tumors expressing estrogen and progesterone receptors. In obese patients, altered levels of several inflammatory mediators regulating aromatase and estrogen expression are one of the mechanisms responsible of increase breast cancer risk. Growing attention has also been paid to the local adipose inflammation and the role played by macrophages as determinants of breast cancer risk recurrence and prognosis. The inflammation-obesity axis offers different molecular signaling pathways for therapeutic interventions and potential pharmacological targets. The increasing rate of obesity worldwide associated with the recent findings linking inflammation and breast cancer urge further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Obesity and cardiac cachexia in chronic heart failure].

PubMed

Clauser, M; Altenberger, J

2013-09-01

Obesity as well as cardiac cachexia in heart failure patients are not fully understood and therefore of high scientific interest. Obesity as a common risk factor for cardiovascular disease is associated with a high mortality. In contrast obesity in patients suffering from chronic heart failure seems to be accompanied with a favorable outcome in contrast to people with normal weight, known as the obesity paradox. In the last decade there has been growing interest in cachexia, which is common in advanced stages of chronic diseases, such as heart failure, chronic obstructive pulmonary disease (COPD), cancer and renal failure and is associated with a poor prognosis. Until now cachexia has been underdiagnosed and undertreated. This review discusses the complex underlying pathomechanisms as well as potential therapeutic approaches.

The impact of obesity in urology.

PubMed

Mydlo, Jack H

2004-05-01

The incidence and progression of urologic diseases, as well as several urologic cancers.depend on many interrelated factors, such as obesity, diet, genetics, environment, age, and the immune system. Obesity is a risk factor for stress urinary incontinence, ED, infertility, and renal calculi. Numerous publications have demonstrated that a high dietary intake of fat increases prostate cancer risk, although the mechanisms are not clear. Although some reports may demonstrate an association between obesity and prostate cancer, it may be hard to establish because, in general, men with obesity have a high-fat diet. Obesity, recurrent urinary tract infections, increased intake of protein and fried foods, and female sex seem to increase the risk of renal cancer. Environmental toxins seem to be the major factors affecting the incidence of bladder cancers. Thus, dietary modification and other public health measures directed at reducing weight may reduce the incidence of urologic illnesses. More studies are necessary to determine the therapeutic effects of weight loss and dietary modification on the incidence and progression of urologic tumors.

Obesity and skin and soft tissue infections: how to optimize antimicrobial usage for prevention and treatment?

PubMed

Grupper, Mordechai; Nicolau, David P

2017-04-01

Skin and soft tissue infections (SSTIs) are prevalent in the obese population, with rising trend expected. Although numerous antibiotics are available for the prevention and treatment of SSTIs, their characterization in obese patients is not a regulatory mandate. Consequently, information that carries importance for optimizing the dosing regimen in the obese population may not be readily available. This review focuses on the most recent pharmacokinetic and pharmacodynamic data on this topic with attention to cefazolin for surgical prophylaxis as well as antibiotics that are active against methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the implications for optimizing SSTIs prevention and treatment in the obese population will also be discussed. On the basis of pharmacokinetic/pharmacodynamic considerations, most studies found a perioperative prophylactic cefazolin regimen of 2 g to be reasonable in the case of obese patients undergoing cesarean delivery or bariatric surgery. There is general paucity of data regarding the pharmacokinetic/pharmacodynamic characteristics of antimicrobials active against MRSA in obese patients, especially for the target tissue. Therapeutic drug monitoring has been correlated with pharmacokinetic/pharmacodynamic optimization for vancomycin and teicoplanin, and should be used in these cases. There is more supportive evidence for the use of oxazolidinones (linezolid and tedizolid), daptomycin and lipoglycopeptides (telavancin, dalbavancin and oritavancin) in the management of SSTIs in this population. The pharmacokinetic/pharmacodynamic approach, which can be used as a basis or supplement to clinical trials, provides valuable data and decision-making tools for optimizing regimens used for both prevention and treatment of SSTIs in the obese population. Important pharmacokinetic/pharmacodynamic characteristics of antibiotics, such as the penetration into the subcutaneous tissue and the probability of reaching the

Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications.

PubMed

Lugogo, Njira; Francisco, Dave; Addison, Kenneth J; Manne, Akarsh; Pederson, William; Ingram, Jennifer L; Green, Cynthia L; Suratt, Benjamin T; Lee, James J; Sunday, Mary E; Kraft, Monica; Ledford, Julie G

2018-03-01

Eosinophils are prominent in some patients with asthma and are increased in the submucosa in a subgroup of obese patients with asthma (OAs). Surfactant protein A (SP-A) modulates host responses to infectious and environmental insults. We sought to determine whether SP-A levels are altered in OAs compared with a control group and to determine the implications of these alterations in SP-A levels in asthmatic patients. Bronchoalveolar lavage fluid from 23 lean, 12 overweight, and 20 obese subjects were examined for SP-A. Mouse tracheal epithelial cells grown at an air-liquid interface were used for mechanistic studies. SP-A -/- mice were challenged in allergen models, and exogenous SP-A therapy was given after the last challenge. Eosinophils were visualized and quantitated in lung parenchyma by means of immunostaining. Significantly less SP-A (P = .002) was detected in samples from OAs compared with those from control subjects. A univariable regression model found SP-A levels were significantly negatively correlated with body mass index (r = -0.33, P = .014), whereas multivariable modeling demonstrated that the correlation depended both on asthma status (P = .017) and the interaction of asthma and body mass index (P = .008). Addition of exogenous TNF-α to mouse tracheal epithelial cells was sufficient to attenuate SP-A and eotaxin secretion. Allergen-challenged SP-A -/- mice that received SP-A therapy had significantly less tissue eosinophilia compared with mice receiving vehicle. SP-A functions as an important mediator in resolving tissue and lavage fluid eosinophilia in allergic mouse models. Decreased levels of SP-A in OAs, which could be due to increased local TNF-α levels, might lead to impaired eosinophil resolution and could contribute to the eosinophilic asthma phenotype. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Screening of anti-obesity agent from herbal mixtures.

PubMed

Roh, Changhyun; Jung, Uhee; Jo, Sung-Kee

2012-03-23

Globally, one in three of the World's adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion--Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl gallate from the herbal composition known as HemoHIM that actively inhibits lipid formation as evidenced by Oil Red O staining and triglyceride (TG) contents in 3T3-L1 adipocytes, suggesting their use as an anti-obesity agent. Furthermore, the amount of glycerol released from cells into the medium had increased by treatment of methyl gallate in a concentration-dependent manner. The present study suggests that a promising anti-obesity agent like methyl gallate might be of therapeutic interest for the treatment of obesity.

The pathophysiology of hypertension in patients with obesity.

PubMed

DeMarco, Vincent G; Aroor, Annayya R; Sowers, James R

2014-06-01

The combination of obesity and hypertension is associated with high morbidity and mortality because it leads to cardiovascular and kidney disease. Potential mechanisms linking obesity to hypertension include dietary factors, metabolic, endothelial and vascular dysfunction, neuroendocrine imbalances, sodium retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and inflammatory responses. Visceral adipose tissue also becomes resistant to insulin and leptin and is the site of altered secretion of molecules and hormones such as adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated cardiovascular disease. Accumulating evidence also suggests that the gut microbiome is important for modulating these mechanisms. Uric acid and altered incretin or dipeptidyl peptidase 4 activity further contribute to the development of hypertension in obesity. The pathophysiology of obesity-related hypertension is especially relevant to premenopausal women with obesity and type 2 diabetes mellitus who are at high risk of developing arterial stiffness and endothelial dysfunction. In this Review we discuss the relationship between obesity and hypertension with special emphasis on potential mechanisms and therapeutic targeting that might be used in a clinical setting.

The pathophysiology of hypertension in patients with obesity

PubMed Central

DeMarco, Vincent G.; Aroor, Annayya R.; Sowers, James R.

2015-01-01

The combination of obesity and hypertension is associated with high morbidity and mortality because it leads to cardiovascular and kidney disease. Potential mechanisms linking obesity to hypertension include dietary factors, metabolic, endothelial and vascular dysfunction, neuroendocrine imbalances, sodium retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and inflammatory responses. Visceral adipose tissue also becomes resistant to insulin and leptin and is the site of altered secretion of molecules and hormones such as adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated cardiovascular disease. Accumulating evidence also suggests that the gut microbiome is important for modulating these mechanisms. Uric acid and altered incretin or dipeptidyl peptidase 4 activity further contribute to the development of hypertension in obesity. The pathophysiology of obesity-related hypertension is especially relevant to premenopausal women with obesity and type 2 diabetes mellitus who are at high risk of developing arterial stiffness and endothelial dysfunction. In this Review we discuss the relationship between obesity and hypertension with special emphasis on potential mechanisms and therapeutic targeting that might be used in a clinical setting. PMID:24732974

Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity

PubMed Central

Zha, Weibin; Edin, Matthew L.; Vendrov, Kimberly C.; Schuck, Robert N.; Lih, Fred B.; Jat, Jawahar Lal; Bradbury, J. Alyce; DeGraff, Laura M.; Hua, Kunjie; Tomer, Kenneth B.; Falck, John R.; Zeldin, Darryl C.; Lee, Craig R.

2014-01-01

Adipogenesis plays a critical role in the initiation and progression of obesity. Although cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have emerged as a potential therapeutic target for cardiometabolic disease, the functional contribution of EETs to adipogenesis and the pathogenesis of obesity remain poorly understood. Our studies demonstrated that induction of adipogenesis in differentiated 3T3-L1 cells (in vitro) and obesity-associated adipose expansion in high-fat diet (HFD)-fed mice (in vivo) significantly dysregulate the CYP epoxygenase pathway and evoke a marked suppression of adipose-derived EET levels. Subsequent in vitro experiments demonstrated that exogenous EET analog administration elicits potent anti-adipogenic effects via inhibition of the early phase of adipogenesis. Furthermore, EET analog administration to mice significantly mitigated HFD-induced weight gain, adipose tissue expansion, pro-adipogenic gene expression, and glucose intolerance. Collectively, these findings suggest that suppression of EET bioavailability in adipose tissue is a key pathological consequence of obesity, and strategies that promote the protective effects of EETs in adipose tissue offer enormous therapeutic potential for obesity and its downstream pathological consequences. PMID:25114171

Craniopharyngioma and hypothalamic injury: latest insights into consequent eating disorders and obesity

PubMed Central

Müller, Hermann L.

2016-01-01

Purpose of review Hypothalamic alterations, pathological or treatment induced, have major impact on prognosis in craniopharyngioma patients mainly because of consequent hypothalamic obesity. Recent insight in molecular genetics, treatment strategies, risk factors and outcomes associated with hypothalamic obesity provide novel therapeutic perspectives. This review includes relevant publications since 2013. Recent findings Recent findings confirm that alterations in posterior hypothalamic areas because of tumour location and/or treatment-related injuries are associated with severe hypothalamic obesity, reduced overall survival and impaired quality of life in long-term survivors of childhood-onset craniopharyngioma. However, eating disorders are observed because of hypothalamic obesity without clear disease-specific patterns. Treatment options for hypothalamic obesity are very limited. Treatment with invasive, nonreversible bariatric methods such as Roux-en-Y gastric bypass is most efficient in weight reduction, but controversial in the paediatric population because of medical, ethical, and legal considerations. Accordingly, treatment in craniopharyngioma should focus on prevention of (further) hypothalamic injury. Presurgical imaging for grading of hypothalamic involvement should be the basis for hypothalamus-sparing strategies conducted by experienced multidisciplinary teams. Summary Until a nonsurgical therapeutic option for hypothalamic obesity for paediatric patients is found, prevention of hypothalamic injury should be the preferred treatment strategy, conducted exclusively by experienced multidisciplinary teams. PMID:26574645

Role of Obesity in Asthma: Mechanisms and Management Strategies.

PubMed

Scott, Hayley A; Wood, Lisa G; Gibson, Peter G

2017-08-01

Obesity is a commonly reported comorbidity in asthma, particularly in severe asthma. Obese asthmatics are highly symptomatic with a poor quality of life, despite using high-dose inhaled corticosteroids. While the clinical manifestations have been documented, the aetiologies of obese-asthma remain unclear. Several potential mechanisms have been proposed, including poor diet quality, physical inactivity and consequent accrual of excess adipose tissue. Each of these factors independently activates inflammatory pathways, potentially exerting effects in the airways. Because the origins of obesity are multifactorial, it is now believed there are multiple obese-asthma phenotypes, with varied aetiologies and clinical consequences. In this review, we will describe the clinical implications of obesity in people with asthma, our current understanding of the mechanisms driving this association and describe recently proposed obese-asthma phenotypes. We will then discuss how asthma management is complicated by obesity, and provide graded recommendations for the management of obesity in this population.

Long-term effects of adolescent obesity: time to act.

PubMed

Reinehr, Thomas

2018-03-01

Obesity in adolescence will probably have major implications not only for the affected adolescents but also for society. Those who have obesity during adolescence usually have obesity into adulthood, which causes many medical and psychological issues that can result in premature death. Furthermore, obesity in adolescents is associated with a range of social problems, including difficulties securing an apprenticeship or a job or finding a partner. Adolescents with obesity are also at increased risk of having children with obesity later in life. All these consequences lead to high costs for the health-care system. Although efficient treatment options are available that have been proven in randomized controlled trials, such as lifestyle interventions for adolescents with obesity and bariatric surgery for adolescents with severe obesity, these interventions frequently fail in clinical practice as treatment adherence is low in adolescents and most adolescents with obesity do not seek medical care. Therefore, improving treatment adherence and identifying treatment barriers are necessary.

Introduction to Genetics and Childhood Obesity: Relevance to Nursing Practice

PubMed Central

Seal, Nuananong

2013-01-01

Purpose The aims for this article are to provide an overview of the current state of research on genetic contributions to the development of childhood obesity and to suggest genetic-focused nursing practices to prevent childhood obesity. Organizing Constructs Genetic epidemiology of childhood obesity, modes to identifying obesity genes, types of human obesity genes, and nursing implications are discussed. Clinical Relevance The successful integration of genetics into nursing practice will provide opportunities for nurses to participate fully as major agents and collaborators in the health care revolution. Conclusions Practicing nurses across the profession will need to become knowledgeable about genetics and take part in obesity prevention through genetic assessment of susceptibility and appropriate environmental interventions. PMID:20798151

Canine and feline obesity: frequently asked questions and their answers.

PubMed

Becvarova, Iveta

2011-11-01

The diagnosis of obesity is simple and warrants intervention because of the association between obesity and increased morbidity. Pet owner commitment, a proper feeding plan, and regular monitoring are the keys to a successful weight loss program. Treatment of obesity involves caloric restriction and/or diet change. Therapeutic weight loss diets differ in fiber, moisture, and digestible carbohydrate contents, and the diet choice should be tailored to the individual patient. Appropriate feeding management is equally important. To protect against the recurrence of obesity, owners should be educated on how to monitor body condition score and adjust the feeding program to maintain proper body condition.

Criteria used to judge obese persons in the workplace.

PubMed

Popovich, P M; Everton, W J; Campbell, K L; Godinho, R M; Kramer, K M; Mangan, M R

1997-12-01

Researchers have speculated that employers are less likely to hire obese persons for more publicly visible jobs, although this hypothesis remains untested. In the present study, 54 undergraduate students rated 40 jobs on several items, including the likelihood they would hire an obese person for each job. Multidimensional scaling showed a one-dimensional solution, labeled as physical activity, with participants less likely to hire obese persons for more active jobs. For hiring likelihood ratings for jobs at either end of the dimension appear to be most similar for men and individuals with more positive attitudes toward obese persons versus women and individuals with more negative attitudes toward obese persons. Implications for both theory and practice are discussed.

Results and Implications of a Problem-Solving Treatment Program for Obesity.

ERIC Educational Resources Information Center

Mahoney, B. K.; And Others

Data are from a large scale experimental study which was designed to evaluate a multimethod problem solving approach to obesity. Obese adult volunteers (N=90) were randomly assigned to three groups: maximal treatment, minimal treatment, and no treatment control. In the two treatment groups, subjects were exposed to bibliographic material and…

The association between chronic pain and obesity.

PubMed

Okifuji, Akiko; Hare, Bradford D

2015-01-01

Obesity and pain present serious public health concerns in our society. Evidence strongly suggests that comorbid obesity is common in chronic pain conditions, and pain complaints are common in obese individuals. In this paper, we review the association between obesity and pain in the general population as well as chronic pain patients. We also review the relationship between obesity and pain response to noxious stimulation in animals and humans. Based upon the existing research, we present several potential mechanisms that may link the two phenomena, including mechanical/structural factors, chemical mediators, depression, sleep, and lifestyle. We discuss the clinical implications of obesity and pain, focusing on the effect of weight loss, both surgical and noninvasive, on pain. The literature suggests that the two conditions are significant comorbidities, adversely impacting each other. The nature of the relationship however is not likely to be direct, but many interacting factors appear to contribute. Weight loss for obese pain patients appears to be an important aspect of overall pain rehabilitation, although more efforts are needed to determine strategies to maintain long-term benefit.

Lay theories of obesity predict actual body mass.

PubMed

McFerran, Brent; Mukhopadhyay, Anirban

2013-08-01

Obesity is a major public health problem, but despite much research into its causes, scientists have largely neglected to examine laypeople's personal beliefs about it. Such naive beliefs are important because they guide actual goal-directed behaviors. In a series of studies across five countries on three continents, we found that people mainly believed either that obesity is caused by a lack of exercise or that it is caused by a poor diet. Moreover, laypeople who indicted a lack of exercise were more likely to actually be overweight than were those who implicated a poor diet. This effect held even after controlling for several known correlates of body mass index (BMI), thereby explaining previously unexplained variance. We also experimentally demonstrated the mechanism underlying this effect: People who implicated insufficient exercise tended to consume more food than did those who indicted a poor diet. These results suggest that obesity has an important, pervasive, and hitherto overlooked psychological antecedent.

Perceived weight discrimination and obesity.

PubMed

Sutin, Angelina R; Terracciano, Antonio

2013-01-01

Weight discrimination is prevalent in American society. Although associated consistently with psychological and economic outcomes, less is known about whether weight discrimination is associated with longitudinal changes in obesity. The objectives of this research are (1) to test whether weight discrimination is associated with risk of becoming obese (Body Mass Index≥30; BMI) by follow-up among those not obese at baseline, and (2) to test whether weight discrimination is associated with risk of remaining obese at follow-up among those already obese at baseline. Participants were drawn from the Health and Retirement Study, a nationally representative longitudinal survey of community-dwelling US residents. A total of 6,157 participants (58.6% female) completed the discrimination measure and had weight and height available from the 2006 and 2010 assessments. Participants who experienced weight discrimination were approximately 2.5 times more likely to become obese by follow-up (OR = 2.54, 95% CI = 1.58-4.08) and participants who were obese at baseline were three times more likely to remain obese at follow up (OR = 3.20, 95% CI = 2.06-4.97) than those who had not experienced such discrimination. These effects held when controlling for demographic factors (age, sex, ethnicity, education) and when baseline BMI was included as a covariate. These effects were also specific to weight discrimination; other forms of discrimination (e.g., sex, race) were unrelated to risk of obesity at follow-up. The present research demonstrates that, in addition to poorer mental health outcomes, weight discrimination has implications for obesity. Rather than motivating individuals to lose weight, weight discrimination increases risk for obesity.

[Can teenage obesity affect mental health?].

PubMed

Assunção, Maria Cecília Formoso; Muniz, Ludmila Correa; Schäfer, Antônio Augusto; Meller, Fernanda de Oliveira; Carús, Juliana Pires; Quadros, Lenice de Castro Muniz de; Domingues, Lídice Rodrigues; da Silva, Vera Lúcia Schmidt; Gonçalves, Helen; Hallal, Pedro Curi; Menezes, Ana Maria Baptista

2013-09-01

This study evaluated the association between obesity and emotional and behavioral difficulties in adolescents. We studied 4,325 individuals 11 to 15 years of age who were members of the 1993 birth cohort in Pelotas, Rio Grande do Sul State, Brazil. Information on body mass index (BMI), maternal assessment of the adolescents' emotional and behavioral health (Strengths and Difficulties Questionnaire - SDQ), and sociodemographic and behavioral characteristics were used. Gender-stratified analyses were conducted with simple and multivariate linear regression. In the adjusted analysis, obesity only correlated with total SDQ scores in boys. Among the latter, teenage obesity was associated with higher scores on the subscale of relational problems with peers. Given current knowledge on the future implications of obesity and mental health and in dealing with adolescents, studies on gender differences in adolescence may contribute to understanding such associations.

Childhood Obesity and Cognitive Achievement.

PubMed

Black, Nicole; Johnston, David W; Peeters, Anna

2015-09-01

Obese children tend to perform worse academically than normal-weight children. If poor cognitive achievement is truly a consequence of childhood obesity, this relationship has significant policy implications. Therefore, an important question is to what extent can this correlation be explained by other factors that jointly determine obesity and cognitive achievement in childhood? To answer this question, we exploit a rich longitudinal dataset of Australian children, which is linked to national assessments in math and literacy. Using a range of estimators, we find that obesity and body mass index are negatively related to cognitive achievement for boys but not girls. This effect cannot be explained by sociodemographic factors, past cognitive achievement or unobserved time-invariant characteristics and is robust to different measures of adiposity. Given the enormous importance of early human capital development for future well-being and prosperity, this negative effect for boys is concerning and warrants further investigation. Copyright © 2015 John Wiley & Sons, Ltd.

Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease.

PubMed

Cho, Jin Ah; Chinnapen, Daniel J F

2018-03-01

Mucosal surfaces that line our gastrointestinal tract are continuously exposed to trillions of bacteria that form a symbiotic relationship and impact host health and disease. It is only beginning to be understood that the cross-talk between the host and microbiome involve dynamic changes in commensal bacterial population, secretion, and absorption of metabolites between the host and microbiome. As emerging evidence implicates dysbiosis of gut microbiota in the pathology and progression of various diseases such as inflammatory bowel disease, obesity, and allergy, conventional treatments that either overlook the microbiome in the mechanism of action, or eliminate vast populations of microbes via wide-spectrum antibiotics need to be reconsidered. It is also becoming clear the microbiome can influence the body's response to therapeutic treatments for cancers. As such, targeting the microbiome as treatment has garnered much recent attention and excitement from numerous research labs and biotechnology companies. Treatments range from fecal microbial transplantation to precision-guided molecular approaches. Here, we survey recent progress in the development of innovative therapeutics that target the microbiome to treat disease, and highlight key findings in the interplay between host microbes and therapy.

Obesity-Related Hormones in Low-Income Preschool-Age Children: Implications for School Readiness

ERIC Educational Resources Information Center

Miller, Alison L.; Lumeng, Carey N.; Delproposto, Jennifer; Florek, Brian; Wendorf, Kristin; Lumeng, Julie C.

2013-01-01

Mechanisms underlying socioeconomic disparities in school readiness and health outcomes, particularly obesity, among preschool-aged children are complex and poorly understood. Obesity can induce changes in proteins in the circulation that contribute to the negative impact of obesity on health; such changes may relate to cognitive and emotion…

Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea

PubMed Central

Perrini, Sebastio; Quaranta, Vitaliano Nicola; Falcone, Vito Antonio; Kounaki, Stella; Ciavarella, Alessandro; Ficarella, Romina; Barbaro, Maria; Nigro, Pasquale; Carratù, Pierluigi; Natalicchio, Annalisa; Laviola, Luigi; Resta, Onofrio

2017-01-01

BACKGROUND. In obese subjects with obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) may be linked to systemic and adipose tissue inflammation. METHODS. We obtained abdominal subcutaneous adipose tissue biopsies from OSA and non-OSA obese (BMI > 35) subjects at baseline and after 24 weeks (T1) of weight-loss intervention plus continuous positive airway pressure (c-PAP) or weight-loss intervention alone, respectively. OSA subjects were grouped according to good (therapeutic) or poor (subtherapeutic) adherence to c-PAP. RESULTS. At baseline, anthropometric and metabolic parameters, serum cytokines, and adipose tissue mRNA levels of obesity-associated chemokines and inflammatory markers were not different in OSA and non-OSA subjects. At T1, body weight was significantly reduced in all groups. Serum concentrations of IL-2, IL-4, IL-6, MCP-1, PDGFβ, and VEGFα were reduced by therapeutic c-PAP in OSA subjects and remained unaltered in non-OSA and subtherapeutic c-PAP groups. Similarly, adipose tissue mRNA levels of macrophage-specific (CD68, CD36) and ER stress (ATF4, CHOP, ERO-1) gene markers, as well as of IL-6, PDGFβ, and VEGFα, were decreased only in the therapeutic c-PAP group. CONCLUSION. CIH does not represent an additional factor increasing systemic and adipose tissue inflammation in morbid obesity. However, in subjects with OSA, an effective c-PAP therapy improves systemic and obesity-associated inflammatory markers. FUNDING. Ministero dell’Università e della Ricerca and Progetti di Rilevante Interesse Nazionale. PMID:28878129

[Temporal and structural differences in the care of obese and non-obese people in nursing homes].

PubMed

Apelt, G; Ellert, S; Kuhlmey, A; Garms-Homolová, V

2012-08-01

Obesity is a common disease in Germany. Although care facilities are confronted with an increasing number of obese people, the care of them in nursing homes is barely investigated. The present study examines the amount of work using the example of the activity of dressing obese and non-obese nursing home residents and discloses with its temporal and structural differences. In five nursing homes in Berlin a fully structured observational study based on a convenience sample was conducted. 48 nurses were observed while performing the activity of dressing 70 residents aged 65 years and older. The residents' demographic data and medical diagnoses were taken from the nursing records. Information about the functional/cognitive status and pain events were collected by using the interRAI Contact Assessment. Further data regarding the nurses were obtained through face-to-face interviews. The results show a significant correlation between Body Mass Index and the required time of dressing. No correlations exist between age, qualifications and nurses' level of education and the time of dressing. Structural differences in the care of obese and non-obese residents appear by changes of, single activity sequences. The care of the obese residents is associated with increased time requirements and structurally differs from the care of the non-obese residents. This should lead to further research because it has implications for staffing in nursing homes.

Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management.

PubMed

Neeland, Ian J; Poirier, Paul; Després, Jean-Pierre

2018-03-27

The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical

Beyond gut microbiota: understanding obesity and type 2 diabetes.

PubMed

Lau, Eva; Carvalho, Davide; Pina-Vaz, Cidália; Barbosa, José-Adelino; Freitas, Paula

2015-01-01

Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behaviour, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences. Gut microbiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polyssacharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases. The main objective of this review is to address the pathogenic association between gut microbiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.

Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications.

PubMed

Hua, Susan; Cabot, Peter J

2010-09-01

Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics. Copyright 2010 Elsevier Ltd. All rights reserved.

An Overview of Links Between Obesity and Mental Health.

PubMed

Avila, Christian; Holloway, Alison C; Hahn, Margaret K; Morrison, Katherine M; Restivo, Maria; Anglin, Rebecca; Taylor, Valerie H

2015-09-01

The American Medical Association recently recognized obesity as both an illness and a leading cause of preventable death and chronic disease. This association is not only linked to physical health outcomes, however, as obesity has also been extensively associated with mental illness as well. Both obesity and severe mental illness decrease quality of life and are associated with an increase in disability, morbidity, and mortality, and when they occur together, these adverse health outcomes are magnified. Despite educational campaigns, increased awareness, and improved treatment options, the high prevalence of mental illness and comorbid obesity remains a serious problem. This review examines this overlap, highlighting clinical and biological factors that have been linked to this association in order to improve our understanding and help elucidate potential therapeutic avenues.

Lower levels of maternal capital in early life predict offspring obesity in adulthood.

PubMed

Gillette, Meghan T; Lohman, Brenda J; Neppl, Tricia K

2017-05-01

As of 2013, 65% of the world's population lived in countries where overweight/obesity kills more people than being underweight. Evolutionary perspectives provide a holistic understanding of both how and why obesity develops and its long-term implications. To test whether the maternal capital hypothesis, an evolutionary perspective, is viable for explaining the development of obesity in adulthood. Restricted-use data from the National Longitudinal Study of Adolescent Health (Add Health; n = 11 403) was analysed using logistic regressions. The sample included adolescents and their biological mothers. The odds of obesity in adulthood increased by 22% for every standard deviation increase in lack of maternal capital (Exp (B) = 1.22, p < .001). That is, individuals whose mothers were young, of an ethnic minority and had short breastfeeding durations were more likely to be obese in adulthood, even after controlling for other factors in infancy, adolescence and adulthood. The results showed that those whose mothers had lower capital were more prone to later life disease (specifically, obesity). The maternal capital perspective is useful for explaining how and why early life characteristics (including maternal resources) predict obesity in adulthood. Implications of the findings are discussed.

Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide.

PubMed

Neuner, Philippe; Peier, Andrea M; Talamo, Fabio; Ingallinella, Paolo; Lahm, Armin; Barbato, Gaetano; Di Marco, Annalise; Desai, Kunal; Zytko, Karolina; Qian, Ying; Du, Xiaobing; Ricci, Davide; Monteagudo, Edith; Laufer, Ralph; Pocai, Alessandro; Bianchi, Elisabetta; Marsh, Donald J; Pessi, Antonello

2014-01-01

Neuromedin U (NMU) is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes. A key liability of NMU as a therapeutic is its very short half-life in vivo. We show here that conjugation of NMU to human serum albumin (HSA) yields a compound with long circulatory half-life, which maintains full potency at both the peripheral and central NMU receptors. Initial attempts to conjugate NMU via the prevalent strategy of reacting a maleimide derivative of the peptide with the free thiol of Cys34 of HSA met with limited success, because the resulting conjugate was unstable in vivo. Use of a haloacetyl derivative of the peptide led instead to the formation of a metabolically stable conjugate. HSA-NMU displayed long-lasting, potent anorectic, and glucose-normalizing activity. When compared side by side with a previously described PEG conjugate, HSA-NMU proved superior on a molar basis. Collectively, our results reinforce the notion that NMU-based therapeutics are promising candidates for the treatment of obesity and diabetes. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

Obesity as a Socially Defined Disease: Philosophical Considerations and Implications for Policy and Care.

PubMed

Hofmann, Bjørn

2016-03-01

Obesity has generated significant worries amongst health policy makers and has obtained increased attention in health care. Obesity is unanimously defined as a disease in the health care and health policy literature. However, there are pragmatic and not principled reasons for this. This warrants an analysis of obesity according to standard conceptions of disease in the literature of philosophy of medicine. According to theories and definitions of disease referring to (abnormal functioning of) internal processes, obesity is not a disease. Obesity undoubtedly can result in disease, making it a risk factor for disease, but not a disease per se. According to several social conceptions of disease, however, obesity clearly is a disease. Obesity can conflict with aesthetic, moral, or other social norms. Making obesity a "social disease" may very well be a wise health policy, assuring and improving population health, especially if we address the social determinants of obesity, such as the food supply and marketing system. However, applying biomedical solutions to social problems may also have severe side effects. It can result in medicalization and enhance stigmatization and discrimination of persons based on appearance or behavior. Approaching social problems with biomedical means may also serve commercial and professionals' interests more than the health and welfare of individuals; it may make quick fix medical solutions halt more sustainable structural solutions. This urges health insurers, health care professionals, and health policy makers to be cautious. Especially if we want to help and respect persons that we classify and treat as obese.

[Focus of childhood obesity from pediatrics].

PubMed

Hurtado-López, Erika F; Macías-Rosales, Rocío

2014-01-01

The prevalences of overweight and obesity have increased dramatically in the last two decades in the adult and children population. The Organization for Cooperation and Economic Development reported in 2010 that Mexico ranks first worldwide in childhood obesity. The 2006 National Health and Nutrition Survey reported that one of every three teenagers are overweight and obese. In the last decades, pediatric hospitals in different parts of the world reported the prevalence of secondary malnutrition, since in those days overweight and obesity did not represent health problems. Currently, the prevalence of overweight and obesity has been scarcely studied in pediatric hospitals. In the Hospital de Pediatría (Children's Hospital) of the Instituto Mexicano del Seguro Social's Centro Médico Nacional de Occidente it is reported a prevalence of overweight of 15.4 % and obesity of 12.2 %, which reflects a nutritional transition.Due to the high prevalence of overweight and obesity in this pediatric hospital of reference, one could conclude that the pediatrician should be able to make a correct evaluation of the nutritional state, because, if he does not detect these problems, we will be condemning children to suffer from a chronic disease for the rest of their lives, and with all the implications in the short, medium and long term.

Metabolic effects of obesity on reproduction.

PubMed

Pasquali, Renato; Gambineri, Alessandra

2006-05-01

Obese women are characterized by similar comorbidities to men, particularly type 2 diabetes mellitus and cardiovascular diseases. Moreover, they also develop some specific problems, including fertility-related disorders and some hormone-dependent forms of cancer. The relationship between excess body fat and reproductive disturbances appears to be stronger for early-onset obesity. Early onset of obesity, particularly during adolescence, favours the development of menses irregularities, chronic oligo-anovulation and infertility in adulthood. Moreover, obesity in women can increase the risk of miscarriage and impair the outcome of assisted reproductive technologies. The main factor implicated in the association between obesity and fertility-related disorders is insulin excess, which accompanies insulin resistance. Hyperinsulinaemia may be directly responsible for the development of androgen excess, through its effects in reducing sex hormone-binding globulin synthesis and circulating concentrations, and in stimulating ovarian androgen production rates. Androgen excess, in turn, represents one of the major factors leading to altered ovarian physiology and associated ovulatory disturbances. Obesity-associated hyperleptinaemia may represent an additional factor involved in anovulation, not only through the induction of insulin resistance, but also through a direct impairment of ovarian function.

The interplay between obesity and cancer: a fly view

PubMed Central

2016-01-01

ABSTRACT Accumulating epidemiological evidence indicates a strong clinical association between obesity and an increased risk of cancer. The global pandemic of obesity indicates a public health trend towards a substantial increase in cancer incidence and mortality. However, the mechanisms that link obesity to cancer remain incompletely understood. The fruit fly Drosophila melanogaster has been increasingly used to model an expanding spectrum of human diseases. Fly models provide a genetically simpler system that is ideal for use as a first step towards dissecting disease interactions. Recently, the combining of fly models of diet-induced obesity with models of cancer has provided a novel model system in which to study the biological mechanisms that underlie the connections between obesity and cancer. In this Review, I summarize recent advances, made using Drosophila, in our understanding of the interplay between diet, obesity, insulin resistance and cancer. I also discuss how the biological mechanisms and therapeutic targets that have been identified in fly studies could be utilized to develop preventative interventions and treatment strategies for obesity-associated cancers. PMID:27604692

Pharmacological Stimulation of NADH Oxidation Ameliorates Obesity and Related Phenotypes in Mice

PubMed Central

Hwang, Jung Hwan; Kim, Dong Wook; Jo, Eun Jin; Kim, Yong Kyung; Jo, Young Suk; Park, Ji Hoon; Yoo, Sang Ku; Park, Myung Kyu; Kwak, Tae Hwan; Kho, Young Lim; Han, Jin; Choi, Hueng-Sik; Lee, Sang-Hee; Kim, Jin Man; Lee, InKyu; Kyung, Taeyoon; Jang, Cholsoon; Chung, Jongkyeong; Kweon, Gi Ryang; Shong, Minho

2009-01-01

OBJECTIVE Nicotinamide adenine dinucleotides (NAD+ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD+-to-NADH ratio is implicated in metabolic syndrome. However, it is still unknown whether a modulating intracellular NAD+-to-NADH ratio is beneficial in treating metabolic syndrome. We tried to determine whether pharmacological stimulation of NADH oxidation provides therapeutic effects in rodent models of metabolic syndrome. RESEARCH DESIGN AND METHODS We used β-lapachone (βL), a natural substrate of NADH:quinone oxidoreductase 1 (NQO1), to stimulate NADH oxidation. The βL-induced pharmacological effect on cellular energy metabolism was evaluated in cells derived from NQO1-deficient mice. In vivo therapeutic effects of βL on metabolic syndrome were examined in diet-induced obesity (DIO) and ob/ob mice. RESULTS NQO1-dependent NADH oxidation by βL strongly provoked mitochondrial fatty acid oxidation in vitro and in vivo. These effects were accompanied by activation of AMP-activated protein kinase and carnitine palmitoyltransferase and suppression of acetyl-coenzyme A (CoA) carboxylase activity. Consistently, systemic βL administration in rodent models of metabolic syndrome dramatically ameliorated their key symptoms such as increased adiposity, glucose intolerance, dyslipidemia, and fatty liver. The treated mice also showed higher expressions of the genes related to mitochondrial energy metabolism (PPARγ coactivator-1α, nuclear respiratory factor-1) and caloric restriction (Sirt1) consistent with the increased mitochondrial biogenesis and energy expenditure. CONCLUSIONS Pharmacological activation of NADH oxidation by NQO1 resolves obesity and related phenotypes in mice, opening the possibility that it may provide the basis for a new therapy for the treatment of metabolic syndrome. PMID:19136651

The Potential Role of Aerobic Exercise-Induced Pentraxin 3 on Obesity-Related Inflammation and Metabolic Dysregulation.

PubMed

Slusher, Aaron L; Huang, Chun-Jung; Acevedo, Edmund O

2017-01-01

Obesity is defined as the excess accumulation of intra-abdominal body fat, resulting in a state of chronic, low-grade proinflammation that can directly contribute to the development of insulin resistance. Pentraxin 3 (PTX3) is an acute-phase protein that is expressed by a variety of tissue and cell sources and provides an anti-inflammatory property to downregulate the production of proinflammatory cytokines, in particular interleukin-1 beta and tumor necrosis factor alpha. Although PTX3 may therapeutically aid in altering the proinflammatory milieu in obese individuals, and despite elevated expression of PTX3 mRNA observed in adipose tissue, the circulating level of PTX3 is reduced with obesity. Interestingly, aerobic activity has been demonstrated to elevate PTX3 levels. Therefore, the purpose of this review is to discuss the therapeutic potential of PTX3 to positively regulate obesity-related inflammation and discuss the proposition for utilizing aerobic exercise as a nonpharmacological anti-inflammatory treatment strategy to enhance circulating PTX3 concentrations in obese individuals.

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation

PubMed Central

Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

2016-01-01

Objective: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Methods: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Results: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. Conclusions: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation.

PubMed

Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

2016-04-25

This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms

Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity.

PubMed

Zha, Weibin; Edin, Matthew L; Vendrov, Kimberly C; Schuck, Robert N; Lih, Fred B; Jat, Jawahar Lal; Bradbury, J Alyce; DeGraff, Laura M; Hua, Kunjie; Tomer, Kenneth B; Falck, John R; Zeldin, Darryl C; Lee, Craig R

2014-10-01

Adipogenesis plays a critical role in the initiation and progression of obesity. Although cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have emerged as a potential therapeutic target for cardiometabolic disease, the functional contribution of EETs to adipogenesis and the pathogenesis of obesity remain poorly understood. Our studies demonstrated that induction of adipogenesis in differentiated 3T3-L1 cells (in vitro) and obesity-associated adipose expansion in high-fat diet (HFD)-fed mice (in vivo) significantly dysregulate the CYP epoxygenase pathway and evoke a marked suppression of adipose-derived EET levels. Subsequent in vitro experiments demonstrated that exogenous EET analog administration elicits potent anti-adipogenic effects via inhibition of the early phase of adipogenesis. Furthermore, EET analog administration to mice significantly mitigated HFD-induced weight gain, adipose tissue expansion, pro-adipogenic gene expression, and glucose intolerance. Collectively, these findings suggest that suppression of EET bioavailability in adipose tissue is a key pathological consequence of obesity, and strategies that promote the protective effects of EETs in adipose tissue offer enormous therapeutic potential for obesity and its downstream pathological consequences. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Obesity and shift work: chronobiological aspects.

PubMed

Antunes, L C; Levandovski, R; Dantas, G; Caumo, W; Hidalgo, M P

2010-06-01

The present review has the objective of summarising chronobiological aspects of shift work and obesity. There was a systematic search in PubMed databases, using the following descriptors: shift work; obesity; biological clock. Shift work is extremely frequent in several services and industries, in order to systematise the needs for flexibility of the workforce, necessary to optimise productivity and business competitiveness. In developing countries, this population represents a considerable contingent workforce. Recently, studies showed that overweight and obesity are more prevalent in shift workers than day workers. In addition, the literature shows that shift workers seem to gain weight more often than those workers submitted to a usual work day. In conclusion, there is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes and CVD, perhaps as a result of physiological maladaptation to chronically sleeping and eating at abnormal circadian times. The impact of shift work on metabolism supports a possible pathway to the development of obesity and its co-morbities. The present review demonstrated the adverse cardiometabolic implications of circadian misalignment, as occurs chronically with shift workers.

Past, Present, and Future of Pharmacologic Therapy in Obesity.

PubMed

Rodríguez, José E; Campbell, Kendall M

2016-03-01

Medications for obesity management can be divided into 4 groups: antidepressants (naltrexone/bupropion), stimulants (phentermine, phendimetrazine, diethylpropion, phentermine/topiramate), fat blockers (orlistat), and diabetes medications (liraglutide). Each group has specific therapeutic effects, adverse effects, and costs. Two medications are indicated for long-term use in obesity: lorcaserin and orlistat. Other available medications are for short-term use. High cost makes many of these medications inaccessible for underserved and poor patients. Because of misuse potential, many obesity medications are also classified as controlled substances. There are no medications currently approved for use in pregnant or lactating women. Copyright © 2016 Elsevier Inc. All rights reserved.

The Microbial Hypothesis: Contributions of Adenovirus Infection and Metabolic Endotoxaemia to the Pathogenesis of Obesity

PubMed Central

2016-01-01

The global obesity epidemic, dubbed “globesity” by the World Health Organisation, is a pressing public health issue. The aetiology of obesity is multifactorial incorporating both genetic and environmental factors. Recently, epidemiological studies have observed an association between microbes and obesity. Obesity-promoting microbiome and resultant gut barrier disintegration have been implicated as key factors facilitating metabolic endotoxaemia. This is an influx of bacterial endotoxins into the systemic circulation, believed to underpin obesity pathogenesis. Adipocyte dysfunction and subsequent adipokine secretion characterised by low grade inflammation, were conventionally attributed to persistent hyperlipidaemia. They were thought of as pivotal in perpetuating obesity. It is now debated whether infection and endotoxaemia are also implicated in initiating and perpetuating low grade inflammation. The fact that obesity has a prevalence of over 600 million and serves as a risk factor for chronic diseases including cardiovascular disease and type 2 diabetes mellitus is testament to the importance of exploring the role of microbes in obesity pathobiology. It is on this basis that Massachusetts General Hospital is sponsoring the Faecal Microbiota Transplant for Obesity and Metabolism clinical trial, to study the impact of microbiome composition on weight. The association of microbes with obesity, namely, adenovirus infection and metabolic endotoxaemia, is reviewed. PMID:28004036

Obesity and Appetite Control

PubMed Central

Suzuki, Keisuke; Jayasena, Channa N.; Bloom, Stephen R.

2012-01-01

Obesity is one of the major challenges to human health worldwide; however, there are currently no effective pharmacological interventions for obesity. Recent studies have improved our understanding of energy homeostasis by identifying sophisticated neurohumoral networks which convey signals between the brain and gut in order to control food intake. The hypothalamus is a key region which possesses reciprocal connections between the higher cortical centres such as reward-related limbic pathways, and the brainstem. Furthermore, the hypothalamus integrates a number of peripheral signals which modulate food intake and energy expenditure. Gut hormones, such as peptide YY, pancreatic polypeptide, glucagon-like peptide-1, oxyntomodulin, and ghrelin, are modulated by acute food ingestion. In contrast, adiposity signals such as leptin and insulin are implicated in both short- and long-term energy homeostasis. In this paper, we focus on the role of gut hormones and their related neuronal networks (the gut-brain axis) in appetite control, and their potentials as novel therapies for obesity. PMID:22899902

Obesity and appetite control.

PubMed

Suzuki, Keisuke; Jayasena, Channa N; Bloom, Stephen R

2012-01-01

Obesity is one of the major challenges to human health worldwide; however, there are currently no effective pharmacological interventions for obesity. Recent studies have improved our understanding of energy homeostasis by identifying sophisticated neurohumoral networks which convey signals between the brain and gut in order to control food intake. The hypothalamus is a key region which possesses reciprocal connections between the higher cortical centres such as reward-related limbic pathways, and the brainstem. Furthermore, the hypothalamus integrates a number of peripheral signals which modulate food intake and energy expenditure. Gut hormones, such as peptide YY, pancreatic polypeptide, glucagon-like peptide-1, oxyntomodulin, and ghrelin, are modulated by acute food ingestion. In contrast, adiposity signals such as leptin and insulin are implicated in both short- and long-term energy homeostasis. In this paper, we focus on the role of gut hormones and their related neuronal networks (the gut-brain axis) in appetite control, and their potentials as novel therapies for obesity.

The Effects of Obesity on Drug Metabolism in Children.

PubMed

Oeser, Steffen G; Rougee, Luc R A; Collier, Abby C

2015-01-01

Obesity in children is a significant clinical concern. There are many anecdotes and case studies regarding specific reactions of obese children to medications including therapeutic failure, adverse drug reactions and/or requirements for higher weight-adjusted dosing. There isis, however, a lack of basic and clinical data dissecting the mechanisms of these effects on pharmaceutical efficacy and safety. At present it is unknown how much of the difference in drug disposition in obese children can be attributed to obesity, to maturation or to an interaction between the two. Since a major determinant of drug disposition is hepatic metabolism, here we review how obesity alters hepatic drug disposition in children. Basic as well as clinical data summarizing the current knowledge of biochemical, physiological and clinical effects of pediatric obesity on drug disposition are considered. We conclude that there is a dire need for increased research into the direct effects of obesity on absorption, distribution, metabolism and excretion, as well as changes to pharmacokinetic parameters such as bioavailability and clearance. Increased effort in this area may elucidate the effects of obesity on clinical drug disposition with sufficient detail to provide better dosing guidelines where needed for children.

The Role of the Gut Microbiota in Childhood Obesity.

PubMed

Pihl, Andreas Friis; Fonvig, Cilius Esmann; Stjernholm, Theresa; Hansen, Torben; Pedersen, Oluf; Holm, Jens-Christian

2016-08-01

Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism associated with obesity. We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism. The review discusses the potential role of the bacterial component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood obesity. A vast number of variables are influencing the gut microbial ecology (e.g., the host genetics, delivery method, diet, age, environment, and the use of pre-, pro-, and antibiotics); but the exact physiological processes behind these relationships need to be clarified. Exploring the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment.

National Institutes of Health Update: Translating Basic Behavioral Science into New Pediatric Obesity Interventions.

PubMed

Czajkowski, Susan M

2016-06-01

Pediatric obesity increases the risk of later-life obesity and chronic diseases. Basic research to better understand factors associated with excessive weight gain in early life and studies translating research findings into preventive and therapeutic strategies are essential to our ability to better prevent and treat childhood obesity. This overview describes several National Institutes of Health efforts designed to stimulate basic and translational research in childhood obesity prevention and treatment. These examples demonstrate the value of research in early phase translational pediatric obesity research and highlight some promising directions for this important area of research. Published by Elsevier Inc.

Hypothalamic inflammation in obesity and metabolic disease.

PubMed

Jais, Alexander; Brüning, Jens C

2017-01-03

Over the last years, hypothalamic inflammation has been linked to the development and progression of obesity and its sequelae. There is accumulating evidence that this inflammation not only impairs energy balance but also contributes to obesity-associated insulin resistance. Elevated activation of key inflammatory mediators such as JNK and IκB kinase (IKK) occurs rapidly upon consumption of a high-fat diet, even prior to significant weight gain. This activation of hypothalamic inflammatory pathways results in the uncoupling of caloric intake and energy expenditure, fostering overeating and further weight gain. In addition, these inflammatory processes contribute to obesity-associated insulin resistance and deterioration of glucose metabolism via altered neurocircuit functions. An understanding of the contributions of different neuronal and non-neuronal cell types to hypothalamic inflammatory processes, and delineation of the differences and similarities between acute and chronic activation of these inflammatory pathways, will be critical for the development of novel therapeutic strategies for the treatment of obesity and metabolic syndrome.

Predictors and clinical implications of shivering during therapeutic normothermia.

PubMed

Badjatia, Neeraj; Kowalski, Robert G; Schmidt, J Michael; Voorhees, Marc E; Claassen, Jan; Ostapkovich, Noeleen D; Presciutti, Mary; Connolly, E Sander; Palestrant, David; Parra, Augusto; Mayer, Stephan A

2007-01-01

Shivering during induced normothermia (IN) remains a therapeutic limitation. We investigated potential risk factors and clinical implications of shivering during IN. Post hoc analysis was performed on 24 patients enrolled in a clinical trial of an automated surface cooling system to achieve IN. Hyponatremia was defined as serum levels <136 mmol/L and hypomagnesaemia as levels <1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly. Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was documented hourly. Mixed effects modeling was used to determine clinical measures associated with shivering. Generalized estimating equation (GEE) models were used to compare baseline-adjusted repeated-measures GCS scores. About of 24 (39%) patients demonstrated shivering. Shivering was associated with men (67% vs. 21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs. 7%, P = 0.02). The average kcal/h (158 +/- 645 kcal/h vs. 493 +/- 645 kcal/h, P = 0.03) was greater in shivering patients. Shivering was positively associated with increases in heart rate (P < 0.001), respiratory rate (P < 0.001), and kcal/h (P < 0.001). Non-shivering patients showed a greater increase from baseline GCS (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were noted between shiverers and non-shiverers. Men, hyponatremia, and hypomagnesaemia may predispose febrile patients treated with IN to shivering. Shivering dramatically increases the amount of heat transfer required to maintain normothermia, and may be associated with adverse effects on level of consciousness.

Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity

PubMed Central

Timper, Katharina; Brüning, Jens C.

2017-01-01

ABSTRACT The ‘obesity epidemic’ represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed. PMID:28592656

Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity.

PubMed

Timper, Katharina; Brüning, Jens C

2017-06-01

The 'obesity epidemic' represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed. © 2017. Published by The Company of Biologists Ltd.

Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity.

PubMed

Padwal, Raj

2009-10-01

Contrave, under development by Orexigen Therapeutics Inc for the potential treatment of obesity, is an oral, sustained-release combination of the dopamine and norepinephrine reuptake antagonist bupropion and the opioid antagonist naltrexone. The proposed dual mechanism of action of the compound involves complementary stimulation of central melanocortin pathways, resulting in increased energy expenditure and reduced appetite. At the time of publication, Contrave was being assessed in phase III clinical trials. Preliminary data demonstrated placebo-subtracted weight losses of 3 to 7% and improvements in obesity-related comorbidities and cardiovascular risk factors. The primary adverse effect leading to discontinuation of treatment was nausea. Assuming that the results of the Contrave phase III clinical program reaffirm the efficacy and safety of the drug combination, this agent could be approved and launched to become a market leader in the anti-obesity therapeutic arena.

Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity.

PubMed

Karimi, G; Jamaluddin, R; Mohtarrudin, N; Ahmad, Z; Khazaai, H; Parvaneh, M

2017-10-01

Recent studies have reported beneficial effects of specific probiotics on obesity. However, the difference in the anti-obesity effects of probiotics as single species and dual species is still uncertain. Therefore, we aimed to compare the efficacy of single and dual species of bacteria on markers of obesity in high-fat diet-induced obese rats. A total of 40 male Sprague-Dawley rats were assigned to one of five groups of varying diets as follows: standard diet, high fat diet (HFD), HFD supplemented with Lactobacillus casei strain Shirota, HFD supplemented with Bifidobacterium longum and HFD supplemented with a mixture of these two bacterial species. After 15 weeks of supplementation, the animals were examined for changes in body weight, body fat, total count of bacteria in fecal, blood serum lipid profile, leptin, adiponectin and inflammatory biomarkers. Histological analysis of the liver and adipose tissue was performed and the hepatic mRNA expression levels of genes related to lipid metabolism were measured. It was found that probiotic supplementation of either B. longum or a mixture of B. longum and LcS bacteria significantly reduced weight and triglycerides in the HFD groups. Supplementation of B. longum bacteria showed better results in terms of modulating leptin level, fat mass, adipocyte size and lipoprotein lipase expression, as well as increasing adiponectin and peroxisome proliferator-activated receptors-γ expression compared to dual species of bacteria. No significant differences were observed in the total count of fecal bacteria, glucose and inflammatory biomarker levels between supplemented groups. B. longum supplementation in obesity was more beneficial in metabolic profile changes than the mixture species. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease.

PubMed

Börgeson, Emma; Johnson, Andrew M F; Lee, Yun Sok; Till, Andreas; Syed, Gulam Hussain; Ali-Shah, Syed Tasadaque; Guiry, Patrick J; Dalli, Jesmond; Colas, Romain A; Serhan, Charles N; Sharma, Kumar; Godson, Catherine

2015-07-07

The role of inflammation in obesity-related pathologies is well established. We investigated the therapeutic potential of LipoxinA4 (LXA4:5(S),6(R),15(S)-trihydroxy-7E,9E,11Z,13E,-eicosatetraenoic acid) and a synthetic 15(R)-Benzo-LXA4-analog as interventions in a 3-month high-fat diet (HFD; 60% fat)-induced obesity model. Obesity caused distinct pathologies, including impaired glucose tolerance, adipose inflammation, fatty liver, and chronic kidney disease (CKD). Lipoxins (LXs) attenuated obesity-induced CKD, reducing glomerular expansion, mesangial matrix, and urinary H2O2. Furthermore, LXA4 reduced liver weight, serum alanine-aminotransferase, and hepatic triglycerides. LXA4 decreased obesity-induced adipose inflammation, attenuating TNF-α and CD11c(+) M1-macrophages (MΦs), while restoring CD206(+) M2-MΦs and increasing Annexin-A1. LXs did not affect renal or hepatic MΦs, suggesting protection occurred via attenuation of adipose inflammation. LXs restored adipose expression of autophagy markers LC3-II and p62. LX-mediated protection was demonstrable in adiponectin(-/-) mice, suggesting that the mechanism was adiponectin independent. In conclusion, LXs protect against obesity-induced systemic disease, and these data support a novel therapeutic paradigm for treating obesity and associated pathologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Carbon dioxide in carbonated beverages induces ghrelin release and increased food consumption in male rats: Implications on the onset of obesity.

PubMed

Eweis, Dureen Samandar; Abed, Fida; Stiban, Johnny

The dangerous health risks associated with obesity makes it a very serious public health issue. Numerous studies verified a correlation between the increase in obesity and the parallel increase in soft drink consumption among world populations. The effects of one main component in soft drinks namely the carbon dioxide gas has not been studied thoroughly in any previous research. Male rats were subjected to different categories of drinks and evaluated for over a year. Stomach ex vivo experiments were undertaken to evaluate the amount of ghrelin upon different beverage treatments. Moreover, 20 male students were tested for their ghrelin levels after ingestion of different beverages. Here, we show that rats consuming gaseous beverages over a period of around 1 year gain weight at a faster rate than controls on regular degassed carbonated beverage or tap water. This is due to elevated levels of the hunger hormone ghrelin and thus greater food intake in rats drinking carbonated drinks compared to control rats. Moreover, an increase in liver lipid accumulation of rats treated with gaseous drinks is shown opposed to control rats treated with degassed beverage or tap water. In a parallel study, the levels of ghrelin hormone were increased in 20 healthy human males upon drinking carbonated beverages compared to controls. These results implicate a major role for carbon dioxide gas in soft drinks in inducing weight gain and the onset of obesity via ghrelin release and stimulation of the hunger response in male mammals. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Prevalence of Obesity in Adults with Mental Retardation: Implications for Health Promotion and Disease Prevention.

ERIC Educational Resources Information Center

Rimmer, James H.; And Others

1993-01-01

Measurement of obesity among 364 adults with mental retardation indicated that rates of obesity were significantly higher among females than males; subjects with severe mental retardation had the lowest overall rates of obesity; and residents of a state-operated institution had lower obesity rates than group home, family, and Intermediate Care…

Effect of obese and lean Zucker rat sera on human and rat prostate cancer cells: implications in obesity-related prostate tumor biology.

PubMed

Lamarre, Neil S; Ruggieri, Michael R; Braverman, Alan S; Gerstein, Matthew I; Mydlo, Jack H

2007-01-01

Several reports have demonstrated the effects of obesity on prostate cancer. Also several reports have linked expression of vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (FGF-2) to prostate cancer aggressiveness. The objective of this study was to determine whether a difference exists between lean and obese Zucker rat sera on proliferation prostate cancer cell lines, as well as to examine the differences in FGF-2 and VEGF concentrations. Ten-week-old female obese and lean Zucker rat sera were subjected to charcoal stripping and tested for the proliferation of human LNCaP and rat AT3B-1 prostate cancer cells. An acetonitrile extract of the charcoal used to strip the sera was also tested for mitogenicity. VEGF and FGF-2 concentrations were determined by enzyme-linked immunosorbent assay. Both unstripped and charcoal-stripped obese rat sera had a greater mitogenic effect than did the lean sera on the LNCaP cell line. Charcoal stripping of both obese and lean sera reduced the mitogenic effect on the AT3B-1 cell line. The acetonitrile extract of the charcoal used to strip the sera was unable to recover this proliferative effect. The concentration of VEGF was greater in the obese serum than in the lean serum, and charcoal stripping reduced the concentrations of both FGF-2 and VEGF. The finding of greater VEGF in obese rat sera, as well as greater mitogenic responses on human prostate cancer cells in vitro, suggests this as one of the many possible mechanisms involved in obesity-related prostate cancer biology.

OBESITY AND NUTRITION IN ARDS

PubMed Central

Stapleton, Renee D.; Suratt, Benjamin T.

2014-01-01

This chapter collectively discusses two important topics related to patients with ARDS: 1) obesity and its potential contribution to clinical outcomes through proposed biologic mechanisms and 2) current literature on provision of nutrition and micronutrients. The prevalence of obesity is rapidly increasing around the world, and more than one third of Americans are now obese. While obesity is associated with increased morbidity and mortality in the general population, recent literature suggests that among critically ill patients including those with ARDS, the relationship between obesity and outcomes is quite complex. Observational data demonstrate that obese patients may be at greater risk of developing ARDS and of having longer ICU and hospital lengths of stay compared to normal weight patients. However, obesity is also associated with improved survival. Therefore, in contrast to what might be assumed by clinicians, although obesity may confer greater ICU morbidity, it appears to simultaneously decrease mortality. The mechanisms for these findings are not yet clear, but recent biologic data may begin to provide an explanation. Critical illness, and more specifically the acute respiratory distress syndrome (ARDS), is a catabolic state where patients demonstrate a profound inflammatory response, multiple organ dysfunction, and hypermetabolism. This is often accompanied by malnutrition, which can lead to further impairment of immune function and increased morbidity and mortality in critically ill patients. Over the past decade or more, as we have come to better understand immunologic effects of nutrition in critical illness, nutrition has begun to be thought of as therapeutic, rather than purely supportive. Additionally, the concept of pharmaconutrition has emerged. Fortunately, several recent large studies about nutrition in critical care, with some investigations specifically in patients with ARDS, have provided valuable new evidence. PMID:25453416

To be, or not to be obese - that's the challenge: a hypothesis on the cortical inhibition of the hypothalamus and its therapeutical consequences.

PubMed

Kreier, Felix

2010-08-01

the subject will gain weight again. It is suggested that this is why diets do not work in the long term. In anorexic patients, the cortex is fully occupied to control the hypothalamus resulting in extreme weight loss. In obese subjects, the cortex is less disciplined and the hypothalamus will take control again to stimulate positive energy balance. From this viewpoint, the limbic-reward system interacts both with the hypothalamus and the cortex to achieve demands by emotional motivation. The last part of this paper describes a therapeutic strategy based on this hypothesis. We propose a dual approach to fight obesity. First, interventions should be implemented that remind the cortex to control the hypothalamus and second, to stimulate physiological feedback to the hypothalamus. Copyright 2010 Elsevier Ltd. All rights reserved.

Relation of obesity to neural activation in response to food commercials

PubMed Central

Yokum, Sonja; Stice, Eric; Harris, Jennifer L.; Brownell, Kelly D.

2014-01-01

Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. PMID:23576811

Overlapping Neural Endophenotypes in Addiction and Obesity

PubMed Central

Michaud, Andréanne; Vainik, Uku; Garcia-Garcia, Isabel; Dagher, Alain

2017-01-01

Impulsivity refers to a tendency to act rapidly without full consideration of consequences. The trait is thought to result from the interaction between high arousal responses to potential rewards and poor self-control. Studies have suggested that impulsivity confers vulnerability to both addiction and obesity. However, results in this area are unclear, perhaps due to the high phenotypic complexity of addictions and obesity. Focusing on impulsivity, the aim of this review is to tackle the putative overlaps between addiction and obesity in four domains: (1) personality research, (2) neurocognitive tasks, (3) brain imaging, and (4) clinical evidence. We suggest that three impulsivity-related domains are particularly relevant for our understanding of similarities between addiction and obesity: lower self-control (high Disinhibition/low Conscientiousness), reward sensitivity (high Extraversion/Positive Emotionality), and negative affect (high Neuroticism/Negative Emotionality). Neurocognitive studies have shown that obesity and addiction are both associated with increased impulsive decision-making and attention bias in response to drug or food cues, respectively. Mirroring this, obesity and different forms of addiction seem to exhibit similar alterations in functional MRI brain activity in response to reward processing and during self-control tasks. Overall, our review provides an integrative approach to understand those facets of obesity that present similarities to addictive behaviors. In addition, we suggest that therapeutic interventions targeting inhibitory control may represent a promising approach for the prevention and/or treatment of obesity. PMID:28659866

[Role of chronic inflammation in adipose tissue in the pathophysiology of obesity].

PubMed

Suganami, Takayoshi; Ogawa, Yoshihiro

2013-02-01

Obesity may be viewed as a chronic low-grade inflammatory disease as well as a metabolic disease. Evidence has accumulated suggesting that chronic inflammation in adipose tissue leads to dramatic changes in number and cell type of stromal cells during the course of obesity, which is referred to as"adipose tissue remodeling". Among stromal cells, macrophages in obese adipose tissue are considered to be crucial for adipose tissue inflammation, which results in dysregulated adipocytokine production and ectopic fat accumulation. Understanding the molecular mechanism underlying adipose tissue inflammation would contribute to the identification of novel therapeutic strategies to prevent or treat obesity-induced metabolic derangements.

Parturition dysfunction in obesity: time to target the pathobiology.

PubMed

Carlson, Nicole S; Hernandez, Teri L; Hurt, K Joseph

2015-12-18

Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity-induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms.

Obesity is associated with genetic variants that alter dopamine availability.

PubMed

Need, A C; Ahmadi, K R; Spector, T D; Goldstein, D B

2006-05-01

Human and animal studies have implicated dopamine in appetite regulation, and family studies have shown that BMI has a strong genetic component. Dopamine availability is controlled largely by three enzymes: COMT, MAOA and MAOB, and by the dopamine transporter SLC6A3, and each gene has a well-characterized functional variant. Here we look at these four functional polymorphisms together, to investigate how heritable variation in dopamine levels influences the risk of obesity in a cohort of 1150, including 240 defined as obese (BMI > or = 30). The COMT and SLC6A3 polymorphisms showed no association with either weight, BMI or obesity risk. We found, however, that both MAOA and MAOB show an excess of the low-activity genotypes in obese individuals (MAOA:chi2= 15.45, p = 0.004; MAOB:chi2= 8.05, p = 0.018). Additionally, the MAOA genotype was significantly associated with both weight (p = 0.0005) and BMI (p = 0.001). When considered together, the 'at risk genotype'--low activity genotypes at both the MAOA and MAOB loci--shows a relative risk for obesity of 5.01. These results have not been replicated and, given the experience of complex trait genetics, warrant caution in interpretation. In implicating both the MAOA and MOAB variants, however, this study provides the first indication that dopamine availability (as opposed to other effects of MAOA) is involved in human obesity. It is therefore a priority to assess the associations in replication datasets.

Research contributions on childhood obesity from a public-private partnership

PubMed Central

2015-01-01

Background Childhood obesity remains a significant global problem with immediate and long-term individual health and societal consequences. Targets for change should include the most potent and predictive factors for obesity at all levels of the personal, social and physical environments. The Michael & Susan Dell Center for Healthy Living (‘the Center’) is a public-private partnership that was developed to address child health issues through research, service, and education. This overview paper introduces a special issue of seven articles on childhood obesity from the Center, and the implications of this research for obesity prevention. Methods and results A review of the literature on public-private partnerships was undertaken and key components of the partnership between the Michael & Susan Dell Foundation and the Center were compared for compatibility. The conceptual framework for Center research, based on social cognitive theory and the social-ecological model, is explained. An overview of papers in this special issue, relative to the conceptual framework, and the implications of this research for childhood obesity prevention, are provided. Conclusions The public-private partnership that created the Michael & Susan Dell Center for Healthy Living has been instrumental in motivating the Center’s academic faculty to focus their research on improvements in child, family and community health through etiologic, epidemiologic, methodologic and intervention research. This special issue extends this work and places particular emphasis on socioeconomic inequalities in addressing the obesity problem in the U.S. and worldwide. PMID:26222489

Obesity: genes, glands or gluttony?

PubMed

Chisholm, D J; Samaras, K; Markovic, T; Carey, D; Lapsys, N; Campbell, L V

1998-01-01

Distribution as well as amount of fat has health implications; central abdominal fat seems to be the major contributor to insulin resistance and risk of diabetes, hypertension and cardiovascular disease. Physical activity and diet affect overall adiposity; moreover, exercise specifically reduces visceral fat. The sexes differ in fat distribution; in particular, pre-menopausal women, despite greater overall adiposity, have much less visceral fat than men. There is a strong genetic determination of overall obesity and central abdominal adiposity. Genes regulating obesity (e.g. Ob) could modulate appetite, satiety, metabolic rate or physical activity. Moderate obesity probably results from interaction between genetic predisposition and an environment of abundant calories and reduced physical activity. Single gene mutations are being identified in a few morbidly obese people; however, the common genetic predisposition for obesity may relate to more subtle variations in regulatory controls. Diet and exercise are effective for some, but the response is often disappointing. Definition of pathways controlling appetite, metabolic rate and lipid metabolism may generate improved pharmacological compounds. Education and availability of lower-energy foods may help, but more radical approaches may be needed, such as environmental restructuring to increase physical activity. The problem is great, but failure will mean intolerably increased health costs.

Implications of mitochondrial uncoupling in skeletal muscle in the development and treatment of obesity.

PubMed

Thrush, A Brianne; Dent, Robert; McPherson, Ruth; Harper, Mary-Ellen

2013-10-01

Understanding the metabolic factors that contribute to obesity development and weight loss success are critical for combating obesity and obesity-related disorders. This review provides an overview of energy metabolism with a particular focus on mitochondrial function in health and in obesity. Mitochondrial proton leak contributes significantly to whole body energy expenditure and the potential role of energy uncoupling in weight loss success is discussed. We provide evidence to support the hypothesis that differences in energy efficiency are important regulators of body weight and weight loss success. © 2013 FEBS.

Sociodemographic and health-lifestyle determinants of obesity risks in Malaysia.

PubMed

Tan, Andrew K G; Dunn, Richard A; Samad, Mohamed Ismail Abdul; Feisul, Mustapha Idzwan

2011-04-01

The purpose of this study was to examine the sociodemographic and health-lifestyle factors that affect the likelihood of obesity among Malaysians. Data were obtained from the Malaysian Non-Communicable Disease Surveillance-1. The cross-sectional population-based survey consisted of 2447 observations, with an obesity prevalence rate of 17.2%. Based on logit regression analysis, the results suggest that obesity risks in Malaysia are affected by gender, education level, family history, health conditions, smoking status, and ethnic backgrounds. Specifically, Malaysians more likely to be obese are females (5.3%), lower educated (0.9%), those with history of family illnesses (4.8%), and nonsmokers (6.4%). However, Chinese (9.3%) and other (5.5%) ethnic groups are less likely to be obese when compared with Malays. Based on these results, several policy implications are discussed vis-à-vis obesity risks in Malaysia.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications.

PubMed

Kraehenmann, Rainer

2017-01-01

A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

PubMed Central

Kraehenmann, Rainer

2017-01-01

Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

Media, social networking, and pediatric obesity.

PubMed

Vandewater, Elizabeth A; Denis, Laurence M

2011-12-01

The 5 years leading up to 2011 witnessed unprecedented transformations in the technology and media available to American consumers. These changes have led to major paradigmatic shifts in the way people think about media, how they use it, and the role they expect it to play in their lives. This article discusses the new media landscape and summarizes the evidence regarding media influences on pediatric obesity. Various effects on pediatric obesity are discussed and some conclusions and implications are provided, including possibilities and future directions for clinical practice and research. Copyright © 2011. Published by Elsevier Inc.

Bacteriophage Procurement for Therapeutic Purposes

PubMed Central

Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

2016-01-01

Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

Childhood obesity and cardiac remodeling: from cardiac structure to myocardial mechanics.

PubMed

Tadic, Marijana; Cuspidi, Cesare

2015-08-01

Epidemic of obesity, especially morbid obesity, among children and adolescents, is a key factor associated with the dramatic increase in prevalence of type 2 diabetes mellitus, arterial hypertension, and metabolic syndrome in this population. Furthermore, childhood obesity represents a very important predictor of obesity in adulthood that is related to cardiovascular and cerebrovascular diseases. Overweight and obesity in children and adolescents are associated with impairment of cardiac structure and function. The majority of studies investigated the influence of obesity on left ventricular remodeling. However, the impact of obesity on the right ventricle, both the atria, and myocardial mechanics has been insufficiently studied. The aim of this review article is to summarize all data about heart remodeling in childhood, from cardiac size, throughout systolic and diastolic function, to myocardial mechanics, using a wide range of mainly echocardiographic techniques and parameters. Additionally, we sought to present current knowledge about the influence of weight loss, achieved by various therapeutic approaches, on the improvement of cardiac geometry, structure, and function in obese children and adolescents.

Social Competence and Obesity in Elementary School

PubMed Central

Cunningham, Solveig A.

2015-01-01

Objectives. We examined the relationship between children’s weight and social competence. Methods. We used data from the third- and fifth-grade waves of the nationally representative Early Childhood Longitudinal Study, Kindergarten Class of 1998–1999 (n = 8346) to examine changes in children’s weight and social competence. Results. Obesity in third grade was not associated with subsequent changes in social competence between third and fifth grade, but social competence in third grade was associated with subsequent development of obesity. Among normal-weight children, having higher social competence in third grade was associated with lower odds of becoming overweight (odds ratio [OR] = 0.80 ±0.09; P < .05) or obese (OR = 0.20 ±0.08; P < .001). In addition, obese children with higher social competence were more likely to lose weight between third and fifth grade (OR = 1.43 ±0.25; P < .05). Conclusions. Obesity and impaired social competence often occur together and have serious implications for children's well-being. More knowledge about how weight and social competence affect one another could inform interventions to promote children’s social development and reduce obesity. PMID:25393191

Interaction of obesity and inflammatory bowel disease

PubMed Central

Harper, Jason W; Zisman, Timothy L

2016-01-01

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management. PMID:27672284

The Potential Role of Aerobic Exercise-Induced Pentraxin 3 on Obesity-Related Inflammation and Metabolic Dysregulation

PubMed Central

Acevedo, Edmund O.

2017-01-01

Obesity is defined as the excess accumulation of intra-abdominal body fat, resulting in a state of chronic, low-grade proinflammation that can directly contribute to the development of insulin resistance. Pentraxin 3 (PTX3) is an acute-phase protein that is expressed by a variety of tissue and cell sources and provides an anti-inflammatory property to downregulate the production of proinflammatory cytokines, in particular interleukin-1 beta and tumor necrosis factor alpha. Although PTX3 may therapeutically aid in altering the proinflammatory milieu in obese individuals, and despite elevated expression of PTX3 mRNA observed in adipose tissue, the circulating level of PTX3 is reduced with obesity. Interestingly, aerobic activity has been demonstrated to elevate PTX3 levels. Therefore, the purpose of this review is to discuss the therapeutic potential of PTX3 to positively regulate obesity-related inflammation and discuss the proposition for utilizing aerobic exercise as a nonpharmacological anti-inflammatory treatment strategy to enhance circulating PTX3 concentrations in obese individuals. PMID:28400677

[Management of children and adolescents with severe obesity].

PubMed

Valerio, G; Licenziati, M R; Tanas, R; Morino, G; Ambruzzi, A M; Balsamo, A; Brambilla, P; Bruzzi, P; Calcaterra, V; Crinò, A; De Falco, R; Franzese, A; Giordano, U; Grugni, G; Iaccarino Idelson, P; Iughetti, L; Maffeis, C; Manco, M; Miraglia Del Giudice, E; Mozzillo, E; Zito, E; Bernasconi, S

2012-08-01

Obesity is a complex public health issue. Recent data indicate the increasing prevalence and severity of obesity in children. Severe obesity is a real chronic condition for the difficulties of long-term clinical treatment, the high drop-out rate, the large burden of health and psychological problems and the high probability of persistence in adulthood. A staged approach for weight management is recommended. The establishment of permanent healthy lifestyle habits aimed at healthy eating, increasing physical activity and reducing sedentary behavior is the first outcome, because of the long-term health benefits of these behaviors. Improvement in medical conditions is also an important sign of long-term health benefits. Rapid weight loss is not pursued, for the implications on growth ad pubertal development and the risk of inducing eating disorders. Children and adolescents with severe obesity should be referred to a pediatric weight management center that has access to a multidisciplinary team with expertise in childhood obesity. This article provides pediatricians a comprehensive and evidence based update on treatment recommendations of severe obesity in children and adolescents.

Overweight and Obese Humans Overeat Away from Home

PubMed Central

de Castro, John M.; King, George A.; Duarte-Gardea, Maria; Gonzalez-Ayala, Salvador; Kooshian, Charles H.

2012-01-01

The built environment has been implicated in the development of the epidemic of obesity. We investigated the differences in the meal patterns of normal weight vs. overweight/obese individuals occurring at home vs. other locations. The location of meals and their size in free-living participants were continuously recorded for 7 consecutive days. Study 1: 81 males and 84 females recorded their intake in 7-d diet diaries and wore a belt that contained a GPS Logger to record their location continuously for 7 consecutive days. Study 2: 388 males and 621 females recorded their intake in diet diaries for 7 consecutive days. In both studies, compared to eating at home, overweight/obese participants ate larger meals away from home in both restaurants and other locations than normal weight participants. Overweight/obese individuals appear to be more responsive to environmental cues for eating away from home. This suggests that the influence of the built environment on the intake of overweight/obese individuals may contribute to the obesity epidemic. PMID:22565154

Obesity, health at every size, and public health policy.

PubMed

Bombak, Andrea

2014-02-01

Obesity is associated with chronic diseases that may negatively affect individuals' health and the sustainability of the health care system. Despite increasing emphasis on obesity as a major health care issue, little progress has been made in its treatment or prevention. Individual approaches to obesity treatment, largely composed of weight-loss dieting, have not proven effective. Little direct evidence supports the notion of reforms to the "obesogenic environment." Both these individualistic and environmental approaches to obesity have important limitations and ethical implications. The low levels of success associated with these approaches may necessitate a new non-weight-centric public health strategy. Evidence is accumulating that a weight-neutral, nutrition- and physical activity-based, Health at Every Size (HAES) approach may be a promising chronic disease-prevention strategy.

Neuroimaging and obesity: current knowledge and future directions

PubMed Central

Carnell, S.; Gibson, C.; Benson, L.; Ochner, C. N.; Geliebter, A.

2011-01-01

Summary Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite-related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications. PMID:21902800

Cognitive flexibility and decision-making in eating disorders and obesity.

PubMed

Perpiñá, Conxa; Segura, Mara; Sánchez-Reales, Sergio

2017-09-01

The aim of the present study was to compare decision-making and cognitive flexibility in patients with disordered eating and weight, ranging from anorexia nervosa to obesity, and a healthy group. Participants were 113 patients (86 with eating disorders and 27 with obesity), and a group of 39 healthy subjects; all completed the Iowa gambling task, the Wisconsin Card Sorting Test and several clinical self-report measures. Eating disordered and obese patients showed impaired performance on the decision-making task, and the obese group showed the worst performance on the set-shifting task. There were no associations between neuropsychological performance and eating or obsessive symptomatology, although significant associations were found with anxiety and depression measures. Considering the executive functions as a transdiagnostic process in ED and obesity could provide explanations for the inability to regulate food intake, present in both ED and obese patients. Implications of these executive impairments in the development and maintenance of ED and obesity are discussed.

Gut Microbiota in Obesity and Undernutrition.

PubMed

de Clercq, Nicolien C; Groen, Albert K; Romijn, Johannes A; Nieuwdorp, Max

2016-11-01

Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the onset and preservation of malnutrition. One of these factors is the gut microbiota, which has been recognized as an important pathophysiologic factor in the development and sustainment of malnutrition. However, to our knowledge, the extent to which the microbiota influences malnutrition has yet to be elucidated. In this review, we summarize the mechanisms via which the gut microbiota may influence energy homeostasis in relation to malnutrition. In addition, we discuss potential therapeutic modalities to ameliorate obesity or undernutrition. © 2016 American Society for Nutrition.

The cost of obesity for nonbariatric inpatient operative procedures in the United States: national cost estimates obese versus nonobese patients.

PubMed

Mason, Rodney J; Moroney, Jolene R; Berne, Thomas V

2013-10-01

To evaluate the economic impact of obesity on hospital costs associated with the commonest nonbariatric, nonobstetrical surgical procedures. Health care costs and obesity are both rising. Nonsurgical costs associated with obesity are well documented but surgical costs are not. National cost estimates were calculated from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database, 2005-2009, for the highest volume nonbariatric nonobstetric procedures. Obesity was identified from the HCUP-NIS severity data file comorbidity index. Costs for obese patients were compared with those for nonobese patients. To control for medical complexity, each obese patient was matched one-to-one with a nonobese patient using age, sex, race, and 28 comorbid defined elements. Of 2,309,699 procedures, 439,8129 (19%) were successfully matched into 2 medically equal groups (obese vs nonobese). Adjusted total hospital costs incurred by obese patients were 3.7% higher with a significantly (P < 0.0001) higher per capita cost of $648 (95% confidence interval [CI]: $556-$736) compared with nonobese patients. Of the 2 major components of hospital costs, length of stay was significantly increased in obese patients (mean difference = 0.0253 days, 95% CI: 0.0225-0.0282) and resource utilization determined by costs per day were greater in obese patients due to an increased number of diagnostic and therapeutic procedures needed postoperatively (odds ratio [OR] = 0.94, 95% CI: 0.93-0.96). Postoperative complications were equivalent in both groups (OR = 0.97, 95% CI: 0.93-1.02). Annual national hospital expenditures for the largest volume surgical procedures is an estimated $160 million higher in obese than in a comparative group of nonobese patients.

Immune function, mitogenicity, and angiogenic growth factor concentrations in lean and obese rodent sera: implications in obesity-related prostate tumor biology.

PubMed

Mydlo, J H; Gerstein, M I; Harris, C F; Braverman, A S

2003-01-01

Some studies suggest that several tumors have a greater incidence in those patients with a high fat diet, such as colon, breast, and prostate. However, we wanted to determine the effects of obesity alone, independent of diet, on the progression of prostate tumor growth. Using a genetic model of obese and lean Zucker rats, we wanted to demonstrate any sera differences in the concentration of basic fibroblast growth factor (FGF-2) and vascular endothelial cell growth factor (VEGF), two important factors involved in the growth and progression of prostate cancer. We also wanted to investigate if there were any differences in immune function between the two sera, which could also account for uninhibited tumor growth, as well as differences in mitogenic stimulation. Female Zucker rat obese and lean sera were analyzed using ELISA assays for FGF-2, VEGF, and macrophage inflammatory protein-1 alpha (MIP-1a), as a measure of macrophage function. In addition, the sera of lean and obese sera were plated on wells growing LNCaP prostate cancer cells to determine differences in mitogenicity. We found a greater concentration of FGF-2 in the sera from obese Zucker rats compared to lean Zucker rats: 6.32+/-0.56 vs 3.48+/-0.34 pg/ml, respectively, P<0.05). We also demonstrated a greater concentration of VEGF in obese rat sera compared to lean sera: 54.4+/-4.1 vs 38.0+/-2.9 pg/mL, respectively, P<0.05). We detected a trend in mitogenic stimulation among LNCaP cells along the higher concentrations of the dose-response curve (0.72+/-0.06 vs 0.51+/-0.5). However, this was not statistically significant. In addition, we did not find a significant difference in MIP-1a macrophage activity levels between sera. To conclude, we speculate that the greater concentrations of VEGF and FGF-2 in the sera of obese rodents vs lean rodents may account for some of the differences seen in obesity-related tumor growth seen in the human condition. However, the lack of any sera differences of immune function

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and heart failure.

PubMed

Jordan, Jens; Toplak, Hermann; Grassi, Guido; Yumuk, Volkan; Kotsis, Vasilios; Engeli, Stefan; Cuspidi, Cesare; Nilsson, Peter M; Finer, Nick; Doehner, Wolfram

2016-09-01

Obese individuals are more likely to develop heart failure. Yet, once heart failure is established, the impact of overweight and obesity on prognosis and survival is unclear. The purpose of this joint scientific statement of the European Association for the Study of Obesity and the European Society of Hypertension is to provide an overview on the current scientific literature on obesity and heart failure in terms of prognosis, mechanisms, and clinical management implications. Moreover, the document identifies open questions that ought to be addressed. The need for more tailored weight management recommendations in heart failure will be emphasized and, in line with the emerging evidence, aims to distinguish between primary disease and secondary outcome prevention. In the primary prevention of heart failure, it appears prudent advising obese individuals to lose or achieve a healthy body weight, especially in those with risk factors such as hypertension or type 2 diabetes. However, there is no evidence from clinical trials to guide weight management in overweight or obese patients with established heart failure. Prospective clinical trials are strongly encouraged.

Obesity in pediatric trauma.

PubMed

Witt, Cordelie E; Arbabi, Saman; Nathens, Avery B; Vavilala, Monica S; Rivara, Frederick P

2017-04-01

The implications of childhood obesity on pediatric trauma outcomes are not clearly established. Anthropomorphic data were recently added to the National Trauma Data Bank (NTDB) Research Datasets, enabling a large, multicenter evaluation of the effect of obesity on pediatric trauma patients. Children ages 2 to 19years who required hospitalization for traumatic injury were identified in the 2013-2014 NTDB Research Datasets. Age and gender-specific body mass indices (BMI) were calculated. Outcomes included injury patterns, operative procedures, complications, and hospital utilization parameters. Data from 149,817 pediatric patients were analyzed; higher BMI percentiles were associated with significantly more extremity injuries, and fewer injuries to the head, abdomen, thorax and spine (p values <0.001). On multivariable analysis, higher BMI percentiles were associated with significantly increased likelihood of death, deep venous thrombosis, pulmonary embolus and pneumonia; although there was no difference in risk of overall complications. Obese children also had significantly longer lengths of stay and more frequent ventilator requirement. Among children admitted after trauma, increased BMI percentile is associated with increased risk of death and potentially preventable complications. These findings suggest that obese children may require different management than nonobese counterparts to prevent complications. Level III; prognosis study. Copyright © 2017 Elsevier Inc. All rights reserved.

Morbidity of severe obesity.

PubMed

Kral, J G

2001-10-01

Although obesity is an easy diagnosis to make, its etiologies, pathophysiology, and symptomatology are extraordinarily complex. Progress in surgical technique and anesthesiological management has substantially improved the safety of performing operations on the severely obese in the last 20 years. These improvements have occurred more or less empirically, without a full understanding of etiology or pathophysiology, although this has advanced concomitantly with improvements in practice. This review has attempted to provide a framework to facilitate progress in the neglected areas of patient selection and choice of operation, in an effort to improve long-term outcome. Despite the disparate etiologies of obesity and its diverse comorbidities and complications, there are unifying interdependent pathogenetic mechanisms of great relevance to the practice of antiobesity surgery. The rate of eating, whether driven by HPA dysfunction, ambient stress, or related hereditary susceptibility factors including the increased energy demands of an expanded body fat mass, participates in a cycle that results in disordered satiety (see Fig. 3). This leads to substrate overload, causing extensive metabolic abnormalities such as atherogenesis, insulin resistance, thrombogenesis, and carcinogenesis. This interpretation of the pathophysiology of obesity ironically accords with the original meaning of the word obesity: "to overeat." The ultimate solution to the problem of obesity--preventing it--will not be forthcoming until the food industry is forced to lower production and change its marketing strategies, as the liquor and tobacco industries in the United States were compelled to do. This cannot occur until the large and fast-growing populations of industrialized nations become educated in the personal implications of the energy principle. Regardless of whether school curricula are modified to prioritize health education, the larger problems of cultural and economic change remain for

Regulation of obesity-related insulin resistance with gut anti-inflammatory agents.

PubMed

Luck, Helen; Tsai, Sue; Chung, Jason; Clemente-Casares, Xavier; Ghazarian, Magar; Revelo, Xavier S; Lei, Helena; Luk, Cynthia T; Shi, Sally Yu; Surendra, Anuradha; Copeland, Julia K; Ahn, Jennifer; Prescott, David; Rasmussen, Brittany A; Chng, Melissa Hui Yen; Engleman, Edgar G; Girardin, Stephen E; Lam, Tony K T; Croitoru, Kenneth; Dunn, Shannon; Philpott, Dana J; Guttman, David S; Woo, Minna; Winer, Shawn; Winer, Daniel A

2015-04-07

Obesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited therapeutically. Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations. Reduction of the gut immune system, using beta7 integrin-deficient mice (Beta7(null)), decreases HFD-induced IR. Treatment of wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters. These beneficial effects are dependent on adaptive and gut immunity and are associated with reduced gut permeability and endotoxemia, decreased visceral adipose tissue inflammation, and improved antigen-specific tolerance to luminal antigens. Thus, the mucosal immune system affects multiple pathways associated with systemic IR and represents a novel therapeutic target in this disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer.

PubMed

Blomain, Erik S; Merlino, Dante J; Pattison, Amanda M; Snook, Adam E; Waldman, Scott A

2016-09-01

Obesity has emerged as a principal cause of mortality worldwide, reflecting comorbidities including cancer risk, particularly in colorectum. Although this relationship is established epidemiologically, molecular mechanisms linking colorectal cancer and obesity continue to be refined. Guanylyl cyclase C (GUCY2C), a membrane-bound guanylyl cyclase expressed in intestinal epithelial cells, binds the paracrine hormones guanylin and uroguanylin, inducing cGMP signaling in colorectum and small intestine, respectively. Guanylin is the most commonly lost gene product in sporadic colorectal cancer, and its universal loss early in transformation silences GUCY2C, a tumor suppressor, disrupting epithelial homeostasis underlying tumorigenesis. In small intestine, eating induces endocrine secretion of uroguanylin, the afferent limb of a novel gut-brain axis that activates hypothalamic GUCY2C-cGMP signaling mediating satiety opposing obesity. Recent studies revealed that diet-induced obesity suppressed guanylin and uroguanylin expression in mice and humans. Hormone loss reflects reversible calorie-induced endoplasmic reticulum stress and the associated unfolded protein response, rather than the endocrine, adipokine, or inflammatory milieu of obesity. Loss of intestinal uroguanylin secretion silences the hypothalamic GUCY2C endocrine axis, creating a feed-forward loop contributing to hyperphagia in obesity. Importantly, calorie-induced guanylin loss silences the GUCY2C-cGMP paracrine axis underlying obesity-induced epithelial dysfunction and colorectal tumorigenesis. Indeed, genetically enforced guanylin replacement eliminated diet-induced intestinal tumorigenesis in mice. Taken together, these observations suggest that GUCY2C hormone axes are at the intersection of obesity and colorectal cancer. Moreover, they suggest that hormone replacement that restores GUCY2C signaling may be a novel therapeutic paradigm to prevent both hyperphagia and intestinal tumorigenesis in obesity

High Intensity Interval Training Increases Natural Killer Cell Number and Function in Obese Breast Cancer-challenged Mice and Obese Women.

PubMed

Barra, Nicole G; Fan, Isabella Y; Gillen, Jenna B; Chew, Marianne; Marcinko, Katarina; Steinberg, Gregory R; Gibala, Martin J; Ashkar, Ali A

2017-12-01

High intensity interval training (HIIT) boosts natural killer (NK) cell number and activity in normal weight breast cancer patients; however, whether this occurs in obese individuals is not well established. The goal of this study was to determine whether HIIT effectively boosts NK cells as a therapeutic strategy against breast cancer in an obese mouse model and in overweight/obese women. Diet induced female C57Bl/6 obese mice were assigned to undergo HIIT for four weeks or remain sedentary. Female participants were subjected to a six weeks HIIT protocol. HIIT mice acclimatized to treadmill running were subsequently injected with 5 × 10 5 polyoma middle T (MT) breast cancer cells intravenously. NK cell number and activation were monitored using flow cytometry, and tumor burden or lipid content evaluated from histological lung and liver tissues, respectively. In both mice and humans, circulating NK cell number and activation (CD3-NK1.1+CD27+ and CD3-CD56+, respectively) markedly increased immediately after HIIT. HIIT obese mice had reduced lung tumor burden compared to controls following MT challenge, and had diminished hepatic lipid deposition despite minimal body weight loss. Our findings demonstrate that HIIT can benefit obese individuals by enhancing NK cell number and activity, reducing tumor burden, and enhancing metabolic health.

Gut Microbiota in Obesity and Undernutrition123

PubMed Central

Groen, Albert K; Romijn, Johannes A; Nieuwdorp, Max

2016-01-01

Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the onset and preservation of malnutrition. One of these factors is the gut microbiota, which has been recognized as an important pathophysiologic factor in the development and sustainment of malnutrition. However, to our knowledge, the extent to which the microbiota influences malnutrition has yet to be elucidated. In this review, we summarize the mechanisms via which the gut microbiota may influence energy homeostasis in relation to malnutrition. In addition, we discuss potential therapeutic modalities to ameliorate obesity or undernutrition. PMID:28140325

Implications of obesity for tendon structure, ultrastructure and biochemistry: a study on Zucker rats.

PubMed

Biancalana, Adriano; Velloso, Lício Augusto; Taboga, Sebastião Roberto; Gomes, Laurecir

2012-02-01

The extracellular matrix consists of collagen, proteoglycans and non-collagen proteins. The incidence of obesity and associated diseases is currently increasing in developed countries. Obesity is considered to be a disease of modern times, and genes predisposing to the disease have been identified in humans and animals. The objective of the present study was to compare the morphological and biochemical aspects of the deep digital flexor tendon of lean (Fa/Fa or Fa/fa) and genetically obese (fa/fa) Zucker rats. Ultrastructural analysis showed the presence of lipid droplets in both groups, whereas disorganized collagen fibril bundles were observed in obese animals. Lean animals presented a larger amount of non-collagen proteins and glycosaminoglycans than obese rats. We propose that the overweight and lesser physical activity in obese animals may have provoked the alterations in the composition and organization of extracellular matrix components but a genetic mechanism cannot be excluded. These alterations might be related to organizational and structural modifications in the collagen bundles that influence the mechanical properties of tendons and the progression to a pathological state. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stress in Obesity and Associated Metabolic and Cardiovascular Disorders

PubMed Central

Holvoet, Paul

2012-01-01

Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity. PMID:24278677

The Intergenerational Cycle of Obesity and Its Implications for Nursing Care of Childbearing Women.

PubMed

Purnell, Molly C; MacKenzie, Meredith A

2016-01-01

Despite intensive focus and interventions at societal and individual levels, more than a third of people in the United States are overweight or obese, and childhood/adolescent obesity rates have dramatically increased during the past three decades. Biomedical research has shown a clear link between the prenatal environment and lifetime adiposity. Children born to overweight and obese women with impaired glucose metabolism show cardiometabolic consequences throughout their life spans that, in turn, affect their children's adiposity. Awareness of this intergenerational cycle of obesity can prompt nurses to intervene in the preconception, prenatal, and postnatal phases. © 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

Pharmacotherapy for obesity: novel agents and paradigms

PubMed Central

Manning, Sean; Pucci, Andrea

2014-01-01

Public health initiatives focused on obesity prevention and lifestyle intervention programmes for patients with obesity have struggled to contain the obesity epidemic to date. In recent years, antiobesity drug therapies have had a limited role in clinical treatment algorithms for patients with obesity. Indeed, a number of high-profile antiobesity drug suspensions have markedly impacted upon the landscape of obesity pharmacotherapy. In this review, we discuss the advent of an increasing array of pharmacotherapeutic agents, which are effective both in inducing weight loss and in maintaining weight loss achieved by lifestyle measures. The development of these drugs as antiobesity agents has followed varying paths, ranging from lorcaserin, a selective serotonin agent, exploiting the beneficial central actions of fenfluramine but without the associated systemic side effects, to liraglutide, a gut hormone already used as a glucose-lowering drug but with appetite-suppressant properties, or the novel drug combination of phentermine/topiramate, two ‘old’ drugs used in lower doses than with previous therapeutic uses, resulting in an additive effect on weight loss and fewer side effects. We summarize the key findings from recent randomized controlled trials of these three drugs. Although these agents lead to clinically important weight loss when used as monotherapy, the use of antiobesity drugs as adjunctive therapy post intensive lifestyle intervention could prove to be the most successful strategy. Moreover, a progressive approach to obesity pharmacotherapy perhaps offers the best opportunity to finally address the obesity crisis on a mass scale. PMID:24790728

Obesity and fractures in postmenopausal women.

PubMed

Premaor, Melissa Orlandin; Pilbrow, Lesley; Tonkin, Carol; Parker, Richard A; Compston, Juliet

2010-02-01

Low body mass index (BMI) is a recognized risk factor for fragility fracture, whereas obesity is widely believed to be protective. As part of a clinical audit of guidance from the National Institute of Health and Clinical Excellence (NICE), we have documented the prevalence of obesity and morbid obesity in postmenopausal women younger than 75 years of age presenting to our Fracture Liaison Service (FLS). Between January 2006 and December 2007, 1005 postmenopausal women aged less than 75 years with a low-trauma fracture were seen in the FLS. Of these women, 805 (80%) underwent assessment of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA), and values for BMI were available in 799. The prevalence of obesity (BMI 30 to 34.9 kg/m(2)) and morbid obesity (BMI > or = 35 kg/m(2)) in this cohort was 19.3% and 8.4%, respectively. Normal BMD was reported in 59.1% of obese and 73.1% of morbidly obese women, and only 11.7% and 4.5%, respectively, had osteoporosis (p < .0001). Multiple regression analysis revealed significant negative associations between hip T-score and age (p < .0001) and significant positive associations with BMI (p < .0001) and previous fracture (p = .001). Our results demonstrate a surprisingly high prevalence of obesity in postmenopausal women presenting to the FLS with low-trauma fracture. Most of these women had normal BMD, as measured by DXA. Our findings have important public heath implications in view of the rapidly rising increase in obesity in many populations and emphasize the need for further studies to establish the pathogenesis of fractures in obese individuals and to determine appropriate preventive strategies. Copyright 2010 American Society for Bone and Mineral Research.

Food Prices and Obesity: Evidence and Policy Implications for Taxes and Subsidies

PubMed Central

Powell, Lisa M; Chaloupka, Frank J

2009-01-01

Context: Pricing policies have been posited as potential policy instruments to address the increasing prevalence of obesity. This article examines whether altering the cost of unhealthy, energy-dense foods, compared with healthy, less-dense foods through the use of fiscal pricing (tax or subsidy) policy instruments would, in fact, change food consumption patterns and overall diet enough to significantly reduce individuals' weight outcomes. Methods: This article examined empirical evidence regarding the food and restaurant price sensitivity of weight outcomes based on a literature search to identify peer-reviewed English-language articles published between 1990 and 2008. Studies were identified from the Medline, PubMed, Econlit, and PAIS databases. The fifteen search combinations used the terms obesity, body mass index, and BMI each in combination with the terms price, prices, tax, taxation, and subsidy. Findings: The studies reviewed showed that when statistically significant associations were found between food and restaurant prices (taxes) and weight outcomes, the effects were generally small in magnitude, although in some cases they were larger for low–socioeconomic status (SES) populations and for those at risk for overweight or obesity. Conclusions: The limited existing evidence suggests that small taxes or subsidies are not likely to produce significant changes in BMI or obesity prevalence but that nontrivial pricing interventions may have some measurable effects on Americans' weight outcomes, particularly for children and adolescents, low-SES populations, and those most at risk for overweight. Additional research is needed to be able to draw strong policy conclusions regarding the effectiveness of fiscal-pricing interventions aimed at reducing obesity. PMID:19298422

Food prices and obesity: evidence and policy implications for taxes and subsidies.

PubMed

Powell, Lisa M; Chaloupka, Frank J

2009-03-01

Pricing policies have been posited as potential policy instruments to address the increasing prevalence of obesity. This article examines whether altering the cost of unhealthy, energy-dense foods, compared with healthy, less-dense foods through the use of fiscal pricing (tax or subsidy) policy instruments would, in fact, change food consumption patterns and overall diet enough to significantly reduce individuals' weight outcomes. This article examined empirical evidence regarding the food and restaurant price sensitivity of weight outcomes based on a literature search to identify peer-reviewed English-language articles published between 1990 and 2008. Studies were identified from the Medline, PubMed, Econlit, and PAIS databases. The fifteen search combinations used the terms obesity, body mass index, and BMI each in combination with the terms price, prices, tax, taxation, and subsidy. The studies reviewed showed that when statistically significant associations were found between food and restaurant prices (taxes) and weight outcomes, the effects were generally small in magnitude, although in some cases they were larger for low-socioeconomic status (SES) populations and for those at risk for overweight or obesity. The limited existing evidence suggests that small taxes or subsidies are not likely to produce significant changes in BMI or obesity prevalence but that nontrivial pricing interventions may have some measurable effects on Americans' weight outcomes, particularly for children and adolescents, low-SES populations, and those most at risk for overweight. Additional research is needed to be able to draw strong policy conclusions regarding the effectiveness of fiscal-pricing interventions aimed at reducing obesity.

Relation of obesity to neural activation in response to food commercials.

PubMed

Gearhardt, Ashley N; Yokum, Sonja; Stice, Eric; Harris, Jennifer L; Brownell, Kelly D

2014-07-01

Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity

PubMed Central

Boughton, C K; Murphy, K G

2013-01-01

Obesity is a major worldwide public health issue. The physiological systems that regulate body weight are thus of great interest as targets for anti-obesity agents. Peptidergic systems are critical to the regulation of energy homeostasis by key regions in the hypothalamus and brainstem. A number of neuropeptide systems have therefore been investigated as potential treatments for obesity. Blocking orexigenic peptide signals such as neuropeptide Y, melanin-concentrating hormone, orexins, relaxin-3 and galanin-like peptide or stimulating anorectic signalling pathways used by peptides such as the melanocortins, ciliary neurotrophic factor and brain-derived neurotrophic factor, are approaches that have shown some promise, but which have also highlighted possible concerns. Manipulation of central peptidergic systems poses a number of therapeutic problems, including brain access and side effects. Given that the homeostatic defence of body weight may limit the effectiveness of any single-target therapy developed, a combination therapy approach may offer the best hope for the effective prevention and treatment of obesity. LINKED ARTICLES This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 PMID:23121386

Endogenous Opioid Mechanisms Are Implicated in Obesity and Weight Loss in Humans.

PubMed

Burghardt, Paul R; Rothberg, Amy E; Dykhuis, Kate E; Burant, Charles F; Zubieta, Jon-Kar

2015-08-01

Successful long-term weight loss is challenging. Brain endogenous opioid systems regulate associated processes; however, their role in the maintenance of weight loss has not been adequately explored in humans. In a preliminary study, the objective was to assess central μ-opioid receptor (MOR) system involvement in eating behaviors and their relationship to long-term maintenance of weight loss. This was a case-control study with follow-up of the treatment group at 1 year after intervention. The study was conducted at a tertiary care university medical center. Lean healthy (n = 7) and chronically obese (n = 7) men matched for age and ethnicity participated in the study. MOR availability measures were acquired with positron emission tomography and [(11)C]carfentanil. Lean healthy men were scanned twice under both fasted and fed conditions. Obese men were placed on a very low-calorie diet to achieve 15% weight loss from baseline weight and underwent two positron emission tomography scans before and two after weight loss, incorporating both fasted and fed states. Brain MOR availability and activation were measured by reductions in MOR availability (nondisplaceable binding potential) from the fed compared with the fasted-state scans. Baseline MOR nondisplaceable binding potential was reduced in obese compared with the lean and partially recovered obese after weight loss in regions that regulate homeostatic, hedonic, and emotional responses to feeding. Reductions in negative affect and feeding-induced MOR system activation in the right temporal pole were highly correlated in leans but not in obese men. A trend for an association between MOR activation in the right temporal pole before weight loss and weight regain 1 year was found. Although these preliminary studies have a small sample size, these results suggest that obesity and diet-induced weight loss impact central MOR binding and endogenous opioid system function. MOR system activation in response to an acute meal

Maternal obesity and neurodevelopmental and psychiatric disorders in offspring

PubMed Central

Edlow, Andrea G.

2017-01-01

There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. PMID:27684946

Electronic Gaming and the Obesity Crisis

ERIC Educational Resources Information Center

Calvert, Sandra L.; Staiano, Amanda E.; Bond, Bradley J.

2013-01-01

Children and adolescents in the United States and in many countries are projected to have shorter life spans than their parents, partly because of the obesity crisis engulfing the developed world. Exposure to electronic media is often implicated in this crisis because media use, including electronic game play, may promote sedentary behavior and…

Metabolomics Reveals that Momordica charantia Attenuates Metabolic Changes in Experimental Obesity.

PubMed

Gong, Zhi-Gang; Zhang, Jianbing; Xu, Yong-Jiang

2017-02-01

Momordica charantia L., also known as bitter melon, has been shown to ameliorate obesity and insulin resistance. However, metabolic changes regulated by M. charantia in obesity are not clearly understood. In this study, serums obtained from obese and M. charantia-treated mice were analyzed by using gas and liquid chromatography-mass spectrometry, and multivariate statistical analysis was performed by Orthogonal partial least squares discriminant analysis. The results from this study indicated that body weight fat and insulin levels of obese mice are dramatically suppressed by 8 weeks of dietary supplementation of M. charantia. Metabolomic data revealed that overproductions of energy and nutrient metabolism in obese mice were restored by M. charantia treatment. The antiinflammatory and inhibition of insulin resistance effect of M. charantia in obesity was illustrated with the restoration of free fatty acids and eicosanoids. The findings achieved in this study further strengthen the therapeutic value of using M. charantia to treat obesity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Targeting the gut microbiome to treat the osteoarthritis of obesity.

PubMed

Schott, Eric M; Farnsworth, Christopher W; Grier, Alex; Lillis, Jacquelyn A; Soniwala, Sarah; Dadourian, Gregory H; Bell, Richard D; Doolittle, Madison L; Villani, David A; Awad, Hani; Ketz, John P; Kamal, Fadia; Ackert-Bicknell, Cheryl; Ashton, John M; Gill, Steven R; Mooney, Robert A; Zuscik, Michael J

2018-04-19

Obesity is a risk factor for osteoarthritis (OA), the greatest cause of disability in the US. The impact of obesity on OA is driven by systemic inflammation, and increased systemic inflammation is now understood to be caused by gut microbiome dysbiosis. Oligofructose, a nondigestible prebiotic fiber, can restore a lean gut microbial community profile in the context of obesity, suggesting a potentially novel approach to treat the OA of obesity. Here, we report that - compared with the lean murine gut - obesity is associated with loss of beneficial Bifidobacteria, while key proinflammatory species gain in abundance. A downstream systemic inflammatory signature culminates with macrophage migration to the synovium and accelerated knee OA. Oligofructose supplementation restores the lean gut microbiome in obese mice, in part, by supporting key commensal microflora, particularly Bifidobacterium pseudolongum. This is associated with reduced inflammation in the colon, circulation, and knee and protection from OA. This observation of a gut microbiome-OA connection sets the stage for discovery of potentially new OA therapeutics involving strategic manipulation of specific microbial species inhabiting the intestinal space.

Targeting the gut microbiome to treat the osteoarthritis of obesity

PubMed Central

Schott, Eric M.; Farnsworth, Christopher W.; Grier, Alex; Lillis, Jacquelyn A.; Soniwala, Sarah; Dadourian, Gregory H.; Bell, Richard D.; Doolittle, Madison L.; Villani, David A.; Ketz, John P.; Kamal, Fadia; Ackert-Bicknell, Cheryl; Ashton, John M.; Gill, Steven R.; Mooney, Robert A.

2018-01-01

Obesity is a risk factor for osteoarthritis (OA), the greatest cause of disability in the US. The impact of obesity on OA is driven by systemic inflammation, and increased systemic inflammation is now understood to be caused by gut microbiome dysbiosis. Oligofructose, a nondigestible prebiotic fiber, can restore a lean gut microbial community profile in the context of obesity, suggesting a potentially novel approach to treat the OA of obesity. Here, we report that — compared with the lean murine gut — obesity is associated with loss of beneficial Bifidobacteria, while key proinflammatory species gain in abundance. A downstream systemic inflammatory signature culminates with macrophage migration to the synovium and accelerated knee OA. Oligofructose supplementation restores the lean gut microbiome in obese mice, in part, by supporting key commensal microflora, particularly Bifidobacterium pseudolongum. This is associated with reduced inflammation in the colon, circulation, and knee and protection from OA. This observation of a gut microbiome–OA connection sets the stage for discovery of potentially new OA therapeutics involving strategic manipulation of specific microbial species inhabiting the intestinal space. PMID:29669931

Pathophysiology of hypertension in obese children: a systematic review.

PubMed

Wirix, A J G; Kaspers, P J; Nauta, J; Chinapaw, M J M; Kist-van Holthe, J E

2015-10-01

Hypertension is increasingly common in overweight and obese children. The mechanisms behind the development of hypertension in obesity are complex, and evidence is limited. In order to effectively treat obese children for hypertension, it is important to have a deeper understanding of the pathophysiology of hypertension in obese children. The present review summarizes the main factors associated with hypertension in obese children and discusses their potential role in its pathophysiology. Systematic searches were conducted in PubMed and EMBASE for articles published up to October 2014. In total, 60 relevant studies were included. The methodological quality of the included studies ranged from weak to strong. Several factors important in the development of hypertension in obese children have been suggested, including endocrine determinants, such as corticosteroids and adipokines, sympathetic nervous system activity, disturbed sodium homeostasis, as well as oxidative stress, inflammation and endothelial dysfunction. Understanding the pathophysiology of hypertension in overweight and obese children is important and could have implications for its screening and treatment. Based on solely cross-sectional observational studies, it is impossible to infer causality. Longitudinal studies of high methodological quality are needed to gain more insight into the complex mechanisms behind the development of hypertension in obese children. © 2015 World Obesity.

Transcriptome analysis reveals the role of glutaredoxin 3 in cardiac energy metabolism in obese mice

USDA-ARS?s Scientific Manuscript database

Obesity has been considered an independent risk factor for many cardiovascular diseases (CVD) including heart failure. Recent epidemiological studies; however, implicate that heart failure patients with mild obesity have a better prognosis than their leaner counterparts. The underlying mechanism(s) ...

Therapeutic Role of Rifaximin in Inflammatory Bowel Disease: Clinical Implication of Human Pregnane X Receptor Activation

PubMed Central

Cheng, Jie; Shah, Yatrik M.; Ma, Xiaochao; Pang, Xiaoyan; Tanaka, Toshiya; Kodama, Tatsuhiko; Krausz, Kristopher W.

2010-01-01

Human pregnane X receptor (PXR) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a human PXR activator, is in clinical trials for treatment of IBD and has demonstrated efficacy in Crohn's disease and active ulcerative colitis. In the current study, the protective and therapeutic role of rifaximin in IBD and its respective mechanism were investigated. PXR-humanized (hPXR), wild-type, and Pxr-null mice were treated with rifaximin in the dextran sulfate sodium (DSS)-induced and trinitrobenzene sulfonic acid (TNBS)-induced IBD models to determine the protective function of human PXR activation in IBD. The therapeutic role of rifaximin was further evaluated in DSS-treated hPXR and Pxr-null mice. Results demonstrated that preadministration of rifaximin ameliorated the clinical hallmarks of colitis in DSS- and TNBS-treated hPXR mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. In addition, higher survival rates and recovery from colitis symptoms were observed in hPXR mice, but not in Pxr-null mice, when rifaximin was administered after the onset of symptoms. Nuclear factor κB (NF-κB) target genes were markedly down-regulated in hPXR mice by rifaximin treatment. In vitro NF-κB reporter assays demonstrated inhibition of NF-κB activity after rifaximin treatment in colon-derived cell lines expressing hPXR. These findings demonstrated the preventive and therapeutic role of rifaximin on IBD through human PXR-mediated inhibition of the NF-κB signaling cascade, thus suggesting that human PXR may be an effective target for the treatment of IBD. PMID:20627999

Total Oxidant and Antioxidant Status in Prepubertal Children with Obesity.

PubMed

Rowicka, Grażyna; Dyląg, Hanna; Ambroszkiewicz, Jadwiga; Riahi, Agnieszka; Weker, Halina; Chełchowska, Magdalena

2017-01-01

Obesity is accompanied by the formation of oxygen free radicals, whose intensified activity without effective defense mechanisms can lead to oxidative stress and related complications. We evaluated the presence of oxidative stress in obese prepubertal children. The study included 83 healthy children aged 2-10 years (62 with obesity and 21 nonobese controls). Total oxidant capacity (TOC), total antioxidant capacity (TAC), oxidized low-density lipoprotein (ox-LDL), lipid parameters, glucose, and C-reactive protein (CRP) were measured in serum. Oxidative stress index (OSI) was calculated. Serum TOC concentration was significantly higher ( p < 0.05) and TAC concentration was lower ( p < 0.05) in obese children. OSI was higher ( p < 0.01) in obese subjects compared with controls. CRP levels were normal in all children, but median CRP value was higher ( p < 0.01) and HDL cholesterol levels were lower ( p < 0.05) in the obese group. We found a significant negative correlation between TAC and ox-LDL concentrations ( r = -0.27, p < 0.05) in obese children. Furthermore, obesity duration was positively correlated with TOC level ( r = 0.32, p < 0.05) in this group. Obesity-related oxidative stress already occurs in prepubescence. Early obesity diagnosis and the necessary therapeutic activity implementation is a vital strategy for the prophylaxis of free radical damage and related multiorgan complications.

Treatment of obesity in the primary care setting: are we there yet?

PubMed

Terre, Lisa; Hunter, Christine; Poston, Walker S Carlos; Haddock, C Keith; Stewart, Shani A

2007-01-01

Obesity is a significant public health issue in the US constituting an independent risk factor for morbidity and mortality as well as complicating the management of other medical conditions. Yet, traditionally most physicians receive little training in evidence-based obesity interventions. Previous literature suggests many physicians believe they do not have effective tools to address obesity and/or that obesity management is not within their scope of practice. Given the new emphasis from NIH and AAFP urging physicians to conceptualize and treat obesity as a chronic medical condition, we examined obesity-related knowledge and practices among military and civilian primary care physicians. Results were similar across these two physician groups in suggesting many physicians still may be ill-prepared to manage obesity in the primary care setting. Implications for patient care and future research are discussed.

Obesity, Health at Every Size, and Public Health Policy

PubMed Central

2014-01-01

Obesity is associated with chronic diseases that may negatively affect individuals’ health and the sustainability of the health care system. Despite increasing emphasis on obesity as a major health care issue, little progress has been made in its treatment or prevention. Individual approaches to obesity treatment, largely composed of weight-loss dieting, have not proven effective. Little direct evidence supports the notion of reforms to the “obesogenic environment.” Both these individualistic and environmental approaches to obesity have important limitations and ethical implications. The low levels of success associated with these approaches may necessitate a new non–weight-centric public health strategy. Evidence is accumulating that a weight-neutral, nutrition- and physical activity–based, Health at Every Size (HAES) approach may be a promising chronic disease-prevention strategy. PMID:24328657

Pharmacotherapy for obesity in individuals with type 2 diabetes.

PubMed

Chukir, Tariq; Shukla, Alpana P; Saunders, Katherine H; Aronne, Louis J

2018-02-01

Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy. Areas covered: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes. Expert opinion: Obesity is the major pathophysiologic driver of T2DM; conversely 5-10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.

The Role of Bariatric Surgery in the Obese Total Joint Arthroplasty Patient.

PubMed

Hooper, Jessica M; Deshmukh, Ajit J; Schwarzkopf, Ran

2018-07-01

Although bariatric surgery is a proven means of weight loss and treatment of obesity-related comorbidities in morbidly obese patients, it is not yet clear how it affects outcomes after total joint arthroplasty in this high-risk patient population. This article explores the effects of obesity and bariatric surgery on osteoarthritis and total joint arthroplasty, and also discusses the financial and ethical implications of use of bariatric surgery for risk reduction before total joint arthroplasty. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-obesity effects of Arctii Fructus (Arctium lappa) in white/brown adipocytes and high-fat diet-induced obese mice.

PubMed

Han, Yo-Han; Kee, Ji-Ye; Kim, Dae-Seung; Park, Jinbong; Jeong, Mi-Young; Mun, Jung-Geon; Park, Sung-Joo; Lee, Jong-Hyun; Um, Jae-Young; Hong, Seung-Heon

2016-12-07

Arctii Fructus is traditionally used in oriental pharmacies as an anti-inflammatory medicine. Although several studies have shown its anti-inflammatory effects, there have been no reports on its use in obesity related studies. In this study, the anti-obesity effect of Arctii Fructus was investigated in high-fat diet (HFD)-induced obese mice, and the effect was confirmed in white and primary cultured brown adipocytes. Arctii Fructus inhibited weight gain and reduced the mass of white adipose tissue in HFD-induced obese mice. Serum levels of triglyceride and LDL-cholesterol were reduced, and HDL-cholesterol was increased in the Arctii Fructus treated group. In 3T3-L1 cells, a water extract (WAF) and 70% EtOH extract (EtAF) of Arctii Fructus significantly inhibited adipogenesis and suppressed the expression of proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha. In particular, EtAF activated the phosphorylation of AMP-activated protein kinase. On the other hand, uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, known as brown adipocytes specific genes, were increased in primary cultured brown adipocytes by WAF and EtAF. This study shows that Arctii Fructus prevents the development of obesity through the inhibition of white adipocyte differentiation and activation of brown adipocyte differentiation which suggests that Arctii Fructus could be an effective therapeutic for treating or preventing obesity.

Therapeutic Potential of Epigallocatechin Gallate Nanodelivery Systems

PubMed Central

Granja, Andreia; Frias, Iúri; Neves, Ana Rute; Reis, Salette

2017-01-01

Nowadays, the society is facing a large health problem with the rising of new diseases, including cancer, heart diseases, diabetes, neurodegenerative diseases, and obesity. Thus, it is important to invest in substances that enhance the health of the population. In this context, epigallocatechin gallate (EGCG) is a flavonoid found in many plants, especially in tea. Several studies support the notion that EGCG has several benefits in fighting cancer, heart diseases, diabetes, and obesity, among others. Nevertheless, the poor intestinal absorbance and instability of EGCG constitute the main drawback to use this molecule in prevention and therapy. The encapsulation of EGCG in nanocarriers leads to its enhanced stability and higher therapeutic effects. A comprehensive review of studies currently available on the encapsulation of EGCG by means of nanocarriers will be addressed. PMID:28791306

Electronic gaming and the obesity crisis.

PubMed

Calvert, Sandra L; Staiano, Amanda E; Bond, Bradley J

2013-01-01

Children and adolescents in the United States and in many countries are projected to have shorter life spans than their parents, partly because of the obesity crisis engulfing the developed world. Exposure to electronic media is often implicated in this crisis because media use, including electronic game play, may promote sedentary behavior and increase consumption of high-calorie foods and beverages that are low in nutritional value. Electronic games, however, may increase children's physical activity and expose them to healthier foods. We examine the role of electronic games in the pediatric obesity crisis and their contribution to more favorable health outcomes. Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.

Electronic Gaming and the Obesity Crisis

PubMed Central

Calvert, Sandra L.; Staiano, Amanda E.; Bond, Bradley J.

2014-01-01

Children and adolescents in the United States and in many countries are projected to have shorter life spans than their parents, partly because of the obesity crisis engulfing the developed world. Exposure to electronic media is often implicated in this crisis because media use, including electronic game play, may promote sedentary behavior and increase consumption of high-calorie foods and beverages that are low in nutritional value. Electronic games, however, may increase children’s physical activity and expose them to healthier foods. We examine the role of electronic games in the pediatric obesity crisis and their contribution to more favorable health outcomes. PMID:23483693

Obesity Prevention for Children with Developmental Disabilities

PubMed Central

Curtin, Carol; Hubbard, Kristie; Sikich, Linmarie; Bedford, James; Bandini, Linda

2014-01-01

The prevention of obesity in children with DD is a pressing public health issue, with implications for health status, independent living, and quality of life. Substantial evidence suggests that children with developmental disabilities (DD), including those with intellectual disabilities (ID) and autism spectrum disorder (ASD), have a prevalence of obesity at least as high if not higher than their typically developing peers. The paper reviews what is known about the classic and unique risk factors for childhood obesity in these groups of children, including dietary, physical activity, sedentary behavior, and family factors, as well as medication use. We use evidence from the literature to make the case that primary prevention at the individual/family, school and community levels will require tailoring of strategies and adapting existing intervention approaches. PMID:25530916

Educational attainment and obesity: a systematic review.

PubMed

Cohen, A K; Rai, M; Rehkopf, D H; Abrams, B

2013-12-01

Although previous systematic reviews considered the relationship between socioeconomic status and obesity, almost 200 peer-reviewed articles have been published since the last review on that topic, and this paper focuses specifically on education, which has different implications. The authors systematically review the peer-reviewed literature from around the world considering the association between educational attainment and obesity. Databases from public health and medicine, education, psychology, economics, and other social sciences were searched, and articles published in English, French, Portuguese and Spanish were included. This paper includes 289 articles that report on 410 populations in 91 countries. The relationship between educational attainment and obesity was modified by both gender and the country's economic development level: an inverse association was more common in studies of higher-income countries and a positive association was more common in lower-income countries, with stronger social patterning among women. Relatively few studies reported on lower-income countries, controlled for a comprehensive set of potential confounding variables and/or attempted to assess causality through the use of quasi-experimental designs. Future research should address these gaps to understand if the relationship between educational attainment and obesity may be causal, thus supporting education policy as a tool for obesity prevention. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications

PubMed Central

Moran, Elizabeth P.; Wang, Zhongxiao; Chen, Jing; Sapieha, Przemyslaw; Smith, Lois E. H.

2016-01-01

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications. PMID:27473938

Cellular retinoic acid bioavailability in various pathologies and its therapeutic implication.

PubMed

Osanai, Makoto

2017-06-01

Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling molecule in various cell types. We found that RA depletion caused by expression of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that the biological effect of RA on target cells is primarily determined by "cellular RA bioavailability", which is defined as the RA level in an individual cell, rather than by the serum concentration of RA. Consistently, stellate cells store approximately 80% of vitamin A in the body, and the state of cellular RA bioavailability regulates their function. Based on the similarities between stellate cells and astrocytes, we demonstrated that retinal astrocytes regulate tight junction-based endothelial integrity in a paracrine manner. Since diabetic retinopathy is characterized by increased vascular permeability in its early pathogenesis, RA normalized retinal astrocytes that are compromised in diabetes, resulting in suppression of vascular leakiness. RA also attenuated the loss of the epithelial barrier in murine experimental colitis. The concept of "cellular RA bioavailability" in various diseases will be directed at understanding various pathologies caused by RA insufficiency, implying the potential feasibility of a therapeutic strategy targeting the stellate cell system. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Osteosarcopenic obesity and fall prevention strategies.

PubMed

Hita-Contreras, Fidel; Martínez-Amat, Antonio; Cruz-Díaz, David; Pérez-López, Faustino R

2015-02-01

Sarcopenia, obesity, and osteoporosis are three interrelated entities which may share common pathophysiological factors. In the last decades, overall survival has drastically increased. Postmenopausal women, due to their estrogen depletion, are at higher risk of developing any of these three conditions or the three, which is termed osteosarcopenic obesity. One of the most common health problems among these patients is the elevated risk of falls and fractures. Falls and fall-related injuries are one of the major causes of mortality and morbidity in older adults, and have a significant impact on social, economical and health-related costs. Several extrinsic and intrinsic risk factors have been described that play a role in the etiology of falls. A therapeutic approach to osteosarcopenic obesity aimed at the prevention of falls must include several factors, and act on those risk elements which can be effectively modified. An adequate weight-loss diet and a good nutritional intake, with an appropriate amount of vitamin D and the right protein/carbohydrates ratio, may contribute to the prevention of falls. The recommendation of physical exercise, both traditional (resistance or aerobic training) and more recent varieties (Tai Chi, Pilates, body vibration), can improve balance and positively contribute to fall prevention, whether by itself or in combination with other therapeutic strategies. Finally, a pharmacological approach, especially one focused on hormone therapy, has shown to have a positive effect on postmenopausal women's balance, leading to a decreased risk of falls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention

PubMed Central

Roth, Christian L.

2015-01-01

Hypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. Hypothalamic dysfunction can lead to hyperinsulinemia and leptin resistance. This review is focused on HO caused by craniopharyngiomas (CP), which are the most common childhood brain tumors of nonglial origin. Despite excellent overall survival rates, CP patients have substantially reduced quality of life because of significant long-term sequelae, notably severe obesity in about 50% of patients, leading to a high rate of cardiovascular mortality. Recent studies reported that both hyperphagia and decreased energy expenditure can contribute to severe obesity in HO patients. Recognized risk factors for severe obesity include large hypothalamic tumors or lesions affecting several medial and posterior hypothalamic nuclei that impact satiety signaling pathways. Structural damage in these nuclei often lead to hyperphagia, rapid weight gain, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue. To date, most efforts to treat HO have shown disappointing long-term success rates. However, treatments based on the distinct pathophysiology of disturbed energy homeostasis related to CP may offer options for successful interventions in the future. PMID:26371051

Pharmacokinetics of intravenous levofloxacin administered at 750 milligrams in obese adults.

PubMed

Cook, Aaron M; Martin, Craig; Adams, Val R; Morehead, R Scott

2011-07-01

The physiochemical properties of levofloxacin suggest that it is an agent which may exhibit altered pharmacokinetics in obese individuals. The purpose of this study was to describe the pharmacokinetics of a single 750-mg intravenous dose of levofloxacin in both hospitalized and ambulatory obese individuals. The hypothesis was that a standard dose of levofloxacin in obese individuals would achieve serum concentrations likely to be therapeutic. A single levofloxacin dose of 750 mg was infused over 90 min, and seven serial serum samples were subsequently obtained to evaluate the pharmacokinetics after the first dose. The peak concentrations of levofloxacin were comparable to those seen with normal-weight individuals. However, the area under the concentration-time curve and clearance were quite variable. Accelerated clearance was evident in the ambulatory obese individuals. Further investigation of the effects of obesity on the pharmacokinetics of levofloxacin is necessary to ensure optimal dosing.

Epidemiologic transitions: migration and development of obesity and cardiometabolic disease in the developing world.

PubMed

Forrester, Terrence

2013-01-01

For centuries, the challenge has been the maintenance of bodyweight in the face of marginal food availability. Since the industrial revolution, energy expenditure related to economic activity and domestic life has fallen progressively as technological innovation has replaced muscular power with labor-saving devices. This fall in activity energy expenditure however has not been associated over this entire period with population weight gain. In the 1970s and the 1980s, there was an abrupt uptick in the rate of rise of relative weight in industrialized countries followed rapidly by developing countries. This has led to high and increasing rates of overweight and obesity in high-income countries worldwide, but also an alarming inclusion of low- and middle-income populations in this obesity epidemic. The precise drivers of these concurrent epidemics are not agreed, but probably include on the one hand an increase in dietary energy intake resulting from the impact of industrialization and globalization on food availability and price. On the other, there is the facilitating underlying status of a steadily falling activity energy expenditure as muscle power as an input into economic production as well as household and leisure activities has been supplanted. The rise in population weight without accompanying linear growth manifests as obesity. The accretion of fat as well as the response to other environmental exposures during progressive industrialization and modernization has evoked an accompanying epidemic of cardiometabolic pathology that has significant impact on health as well as macroeconomics. Given the power and presumed irreversibility of industrialization and globalization, our ability to reverse these obesity epidemics is heavily dependent on new knowledge being developed which gives insight with prevention and therapeutic implications on the proximal and distal drivers of this progressive positive energy balance. Copyright © 2013 Nestec Ltd., Vevey/S. Karger

Selective Deletion of Leptin Signaling in Endothelial Cells Enhances Neointima Formation and Phenocopies the Vascular Effects of Diet-Induced Obesity in Mice.

PubMed

Hubert, Astrid; Bochenek, Magdalena L; Schütz, Eva; Gogiraju, Rajinikanth; Münzel, Thomas; Schäfer, Katrin

2017-09-01

cardiovascular risk factor obesity may have relevant therapeutic implications. © 2017 American Heart Association, Inc.

Update on the pathophysiological activities of the cardiac molecule cardiotrophin-1 in obesity.

PubMed

Asrih, Mohamed; Mach, François; Quercioli, Alessandra; Dallegri, Franco; Montecucco, Fabrizio

2013-01-01

Cardiotrophin-1 (CT-1) is a heart-targeting cytokine that has been reported to exert a variety of activities also in other organs such as the liver, adipose tissue, and atherosclerotic arteries. CT-1 has been shown to induce these effects via binding to a transmembrane receptor, comprising the leukaemia inhibitory factor receptor (LIFR β ) subunit and the glycoprotein 130 (gp130, a common signal transducer). Both local and systemic concentrations of CT-1 have been shown to potentially play a critical role in obesity. For instance, CT-1 plasma concentrations have been shown to be increased in metabolic syndrome (a cluster disease including obesity) probably due to adipose tissue overexpression. Interestingly, treatment with exogenous CT-1 has been shown to improve lipid and glucose metabolism in animal models of obesity. These benefits might suggest a potential therapeutic role for CT-1. However, beyond its beneficial properties, CT-1 has been also shown to induce some adverse effects, such as cardiac hypertrophy and adipose tissue inflammation. Although scientific evidence is still needed, CT-1 might be considered as a potential example of damage/danger-associated molecular pattern (DAMP) in obesity-related cardiovascular diseases. In this narrative review, we aimed at discussing and updating evidence from basic research on the pathophysiological and potential therapeutic roles of CT-1 in obesity.

The obese gut microbiome across the epidemiologic transition.

PubMed

Dugas, Lara R; Fuller, Miles; Gilbert, Jack; Layden, Brian T

2016-01-01

The obesity epidemic has emerged over the past few decades and is thought to be a result of both genetic and environmental factors. A newly identified factor, the gut microbiota, which is a bacterial ecosystem residing within the gastrointestinal tract of humans, has now been implicated in the obesity epidemic. Importantly, this bacterial community is impacted by external environmental factors through a variety of undefined mechanisms. We focus this review on how the external environment may impact the gut microbiota by considering, the host's geographic location 'human geography', and behavioral factors (diet and physical activity). Moreover, we explore the relationship between the gut microbiota and obesity with these external factors. And finally, we highlight here how an epidemiologic model can be utilized to elucidate causal relationships between the gut microbiota and external environment independently and collectively, and how this will help further define this important new factor in the obesity epidemic.

Iron and obesity in females in the United States.

PubMed

Neymotin, Florence; Sen, Urmimala

2011-01-01

Since the late 1980s, the United States has witnessed a dramatic increase in average BMI levels and the proportion of individuals categorized as obese. Obesity is a major risk factor for a variety of illnesses, and an increase in obesity is, therefore, implicated in increased health-care costs in the United States. These ultimately translate to a major health and economic problem for the United States. The present analysis examines a pathway to increased levels of obesity as of yet almost entirely unexplored. Specifically, we examine the relationship between obesity and iron deficiency via analyses of blood samples. The current analysis employs public-use data files from the continuous National Health and Nutrition Examination Survey (NHANES) (1999-2006) survey to determine the relationship between obesity and an individual's iron blood content. Results suggest a negative relationship between levels of iron blood content and individual BMI after controlling for other individual characteristics. These results hold for nearly all eight panels tested in the ordinary least squares (OLS) regressions.

Abdominal obesity and the metabolic syndrome: a surgeon's perspective.

PubMed

Mathieu, Patrick

2008-09-01

Over the past decade, a major shift in the clinical risk factors in the population undergoing a cardiac surgery has been observed. In the general population, an increasing prevalence of obesity has largely contributed to the development of cardiovascular disorders. Obesity is a heterogeneous condition in which body fat distribution largely determines metabolic perturbations. Consequently, individuals characterized by increased abdominal fat deposition and the so-called metabolic syndrome (MetS) have a higher risk of developing coronary artery disease. Recent studies have also emphasized that visceral obesity is a strong risk factor for the development of heart valve diseases. In fact, individuals characterized by visceral obesity and its metabolic consequences, such as the small dense low-density lipoprotein phenotype, have a faster progression rate of aortic stenosis, which is related to increased valvular inflammation. Furthermore, the degenerative process of implanted bioprostheses is increased in subjects with the MetS and/or diabetes, suggesting that a process akin to atherosclerosis could be involved in the failure of bioprostheses. In addition to being an important risk factor for the development of cardiovascular disorders, the MetS is increasing the operative mortality risk following coronary artery bypass graft surgery. Thus, recent evidence supports visceral obesity as a global risk factor that is affecting the development of many heart disorders, and that is also impacting negatively on the results of patients undergoing surgical treatment for cardiovascular diseases. In the present paper, recent concepts surrounding the MetS and its implications in various cardiovascular disorders are reviewed along with the clinical implications.

Obesity and Kidney Disease: Hidden Consequences of the Epidemic.

PubMed

Kovesdy, Csaba P; Furth, Susan; Zoccali, Carmine

2017-03-01

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes mellitus, cardiovascular disease, and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term. The incidence of obesity-related glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

Measuring food intake in studies of obesity.

PubMed

Lissner, Lauren

2002-12-01

The problem of how to measure habitual food intake in studies of obesity remains an enigma in nutritional research. The existence of obesity-specific underreporting was rather controversial until the advent of the doubly labelled water technique gave credence to previously anecdotal evidence that such a bias does in fact exist. This paper reviews a number of issues relevant to interpreting dietary data in studies involving obesity. Topics covered include: participation biases, normative biases,importance of matching method to study, selective underreporting, and a brief discussion of the potential implications of generalised and selective underreporting in analytical epidemiology. It is concluded that selective underreporting of certain food types by obese individuals would produce consequences in analytical epidemiological studies that are both unpredictable and complex. Since it is becoming increasingly acknowledged that selective reporting error does occur, it is important to emphasise that correction for energy intake is not sufficient to eliminate the biases from this type of error. This is true both for obesity-related selective reporting errors and more universal types of selective underreporting, e.g. foods of low social desirability. Additional research is urgently required to examine the consequences of this type of error.

Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

PubMed

Krishnan, Navasona; Bonham, Christopher A; Rus, Ioana A; Shrestha, Om Kumar; Gauss, Carla M; Haque, Aftabul; Tocilj, Ante; Joshua-Tor, Leemor; Tonks, Nicholas K

2018-01-18

The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

Treatment Preferences Affect the Therapeutic Alliance: Implications for Randomized Controlled Trials

ERIC Educational Resources Information Center

Iacoviello, Brian M.; McCarthy, Kevin Scott; Barrett, Marna S.; Rynn, Moira; Gallop, Robert; Barber, Jacques P.

2007-01-01

The influence of treatment preferences on the development of the therapeutic alliance was investigated. Seventy-five patients were followed while participating in a randomized controlled trial comparing supportive-expressive psychotherapy with sertraline or pill placebo in the treatment of major depressive disorder. Therapeutic alliance was…

Childhood Obesity and Its Impact on the Development of Adolescent PCOS

PubMed Central

Anderson, Amy D.; Solorzano, Christine M. Burt; McCartney, Christopher R.

2014-01-01

Obesity exacerbates the reproductive and metabolic manifestations of polycystic ovary syndrome (PCOS). The symptoms of PCOS often begin in adolescence, and the rising prevalence of peripubertal obesity has prompted concern that the prevalence and severity of adolescent PCOS is increasing in parallel. Recent data have disclosed a high prevalence of hyperandrogenemia among peripubertal adolescents with obesity, suggesting that such girls are indeed at risk for developing PCOS. Obesity may impact the risk of PCOS via insulin resistance and compensatory hyperinsulinemia, which augments ovarian/adrenal androgen production and suppresses sex hormone–binding globulin (SHBG), thereby increasing androgen bioavailability. Altered luteinizing hormone (LH) secretion plays an important role in the pathophysiology of PCOS, and although obesity is generally associated with relative reductions of LH, higher LH appears to be the best predictor of increased free testosterone among peripubertal girls with obesity. Other potential mechanisms of obesity-associated hyperandrogenemia include enhanced androgen production in an expanded fat mass and potential effects of abnormal adipokine/cytokine levels. Adolescents with PCOS are at risk for comorbidities such as metabolic syndrome and impaired glucose tolerance, and concomitant obesity compounds these risks. For all of these reasons, weight loss represents an important therapeutic target in obese adolescents with PCOS. PMID:24715515

Childhood obesity and its impact on the development of adolescent PCOS.

PubMed

Anderson, Amy D; Solorzano, Christine M Burt; McCartney, Christopher R

2014-05-01

Obesity exacerbates the reproductive and metabolic manifestations of polycystic ovary syndrome (PCOS). The symptoms of PCOS often begin in adolescence, and the rising prevalence of peripubertal obesity has prompted concern that the prevalence and severity of adolescent PCOS is increasing in parallel. Recent data have disclosed a high prevalence of hyperandrogenemia among peripubertal adolescents with obesity, suggesting that such girls are indeed at risk for developing PCOS. Obesity may impact the risk of PCOS via insulin resistance and compensatory hyperinsulinemia, which augments ovarian/adrenal androgen production and suppresses sex hormone-binding globulin (SHBG), thereby increasing androgen bioavailability. Altered luteinizing hormone (LH) secretion plays an important role in the pathophysiology of PCOS, and although obesity is generally associated with relative reductions of LH, higher LH appears to be the best predictor of increased free testosterone among peripubertal girls with obesity. Other potential mechanisms of obesity-associated hyperandrogenemia include enhanced androgen production in an expanded fat mass and potential effects of abnormal adipokine/cytokine levels. Adolescents with PCOS are at risk for comorbidities such as metabolic syndrome and impaired glucose tolerance, and concomitant obesity compounds these risks. For all of these reasons, weight loss represents an important therapeutic target in obese adolescents with PCOS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Preventing and treating obesity in pediatrics through physical activity.

PubMed

Graf, Christine

2011-09-01

The prevalence of juvenile obesity is increasing worldwide. Throughout Europe, ca. 20% are affected, in Germany 15%. Many modifiable and nonmodifiable causes have been determined and included, but are not limited to genetic, familiar, and lifestyle factors. In addition, obesity disproportionately affects minority and low socioeconomic status groups. Juvenile obesity increases the risk of having multiple cardiovascular and metabolic diseases, psycho-social problems, and a variety of other co-morbidities. The burden upon the health services cannot yet be estimated. Therefore, there is a need for preventive and therapeutic counter-measures. Until now, most approaches focus on changing the behaviour of individuals in diet and exercise. Based on the existing data researchers agree that programmes should start as early as possible and involve children's environment (family, peers etc.). In conclusion, a positive public health approach including political, environmental, sociocultural, and educational strategies offer the best chance of preventing and reducing juvenile obesity.

Simulation Models of Obesity: A Review of the Literature and Implications for Research and Policy

PubMed Central

Levy, David T.; Mabry, Patricia L.; Wang, Y. Claire; Gortmaker, Steve; Huang, Terry T-K; Marsh, Tim; Moodie, Marj; Swinburn, Boyd

2015-01-01

Simulation models (SMs) combine information from a variety of sources to provide a useful tool for examining how the effects of obesity unfold over time and impact population health. SMs can aid in the understanding of the complex interaction of the drivers of diet and activity and their relation to health outcomes. As emphasized in a recently released report of the Institute or Medicine, SMs can be especially useful for considering the potential impact of an array of policies that will be required to tackle the obesity problem. The purpose of this paper is to present an overview of existing SMs for obesity. First, a background section introduces the different types of models, explains how models are constructed, shows the utility of SMs, and discusses their strengths and weaknesses. Using these typologies, we then briefly review extant obesity SMs. We categorize these models according to their focus: health and economic outcomes, trends in obesity as a function of past trends, physiologically-based behavioral models, environmental contributors to obesity, and policy interventions. Finally, we suggest directions for future research. PMID:20973910

The promise of ghrelin antagonism in obesity treatment.

PubMed

Helmling, Steffen; Jarosch, Florian; Klussmann, Sven

2006-01-01

According to the World Health Organization, 300 million people are clinically obese worldwide. As a major risk factor in the development of life-threatening diseases such as diabetes, cardiovascular disease and certain cancers, obesity is quickly evolving into a serious public health threat on a global scale. This alarming situation calls for the development of effective treatments, including pharmacological intervention. Many biotechnology and pharmaceutical companies have embarked on the endeavor to develop safe new therapeutics for weight loss and durable weight management. Much progress has been made to improve our understanding of the regulation of energy homeostasis, but this knowledge has not yet translated into new medicines. However, it has led to the identification of molecules that promise to be highly interesting targets for therapeutic intervention. One such molecule is the enteric hormone ghrelin. Ghrelin was identified in 1999 as the endogenous ligand for the growth hormone secretagogue-receptor 1a (GHS-R1a). Soon after its discovery ghrelin was shown to increase food intake, downregulate energy expenditure and conserve body fat, causing weight gain and adipogenesis. Unsurprisingly, these findings placed ghrelin and its receptor on the radar screens of many medical researchers in academia and the pharmaceutical industry. The resulting attention has led to a steadily growing body of evidence in support of ghrelin antagonism as a potential means to ameliorate obesity. But the causes for obesity are manifold, and skepticism about the utility of this approach remains. The current review summarizes the arguments for and against ghrelin as a potential antiobesity target and discusses recent pharmaceutical developments to interfere with this exciting pathway. 2006 Prous Science. All rights reserved.

Obesity and kidney disease: from population to basic science and the search for new therapeutic targets.

PubMed

Whaley-Connell, Adam; Sowers, James R

2017-08-01

The global burden of kidney disease is increasing strikingly in parallel with increases in obesity and diabetes. Indeed, chronic kidney disease (CKD) and end-stage renal disease (ESRD) coupled with comorbidities such as obesity, diabetes, and hypertension cost the health care system hundreds of billions of dollars in the US alone. The progression to ESRD in patients with obesity and diabetes continues despite widespread use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) along with aggressive blood pressure and glycemic control in these high-risk populations. Thereby, it is increasingly important to better understand the underlying mechanisms involved in obesity-related CKD in order to develop new strategies that prevent or interrupt the progression of this costly disease. In this context, a key mechanism that drives development and progression of kidney disease in obesity is endothelial dysfunction and associated tubulointerstitial fibrosis. However, the precise interactive mechanisms in the development of aortic and kidney endothelial dysfunction and tubulointerstitial fibrosis remain unclear. Further, strategies specifically targeting kidney fibrosis have yielded inconclusive benefits in human studies. While clinical data support the benefits derived from inhibition of the RAAS, there is a tremendous amount of residual risk for the progression of kidney disease in individuals with obesity and diabetes. There is promising experimental data to suggest that exercise, targeting inflammation and oxidative stress, lowering uric acid, and targeting the mineralocorticoid receptor signaling and/or sodium channel inhibition could improve tubulointerstitial fibrosis and mitigate progression of kidney disease in persons with obesity and diabetes. Published by Elsevier Inc.

High Intensity Interval Training Increases Natural Killer Cell Number and Function in Obese Breast Cancer-challenged Mice and Obese Women

PubMed Central

Barra, Nicole G.; Fan, Isabella Y.; Gillen, Jenna B.; Chew, Marianne; Marcinko, Katarina; Steinberg, Gregory R.; Gibala, Martin J.; Ashkar, Ali A.

2017-01-01

High intensity interval training (HIIT) boosts natural killer (NK) cell number and activity in normal weight breast cancer patients; however, whether this occurs in obese individuals is not well established. The goal of this study was to determine whether HIIT effectively boosts NK cells as a therapeutic strategy against breast cancer in an obese mouse model and in overweight/obese women. Diet induced female C57Bl/6 obese mice were assigned to undergo HIIT for four weeks or remain sedentary. Female participants were subjected to a six weeks HIIT protocol. HIIT mice acclimatized to treadmill running were subsequently injected with 5 × 105 polyoma middle T (MT) breast cancer cells intravenously. NK cell number and activation were monitored using flow cytometry, and tumor burden or lipid content evaluated from histological lung and liver tissues, respectively. In both mice and humans, circulating NK cell number and activation (CD3−NK1.1+CD27+ and CD3−CD56+, respectively) markedly increased immediately after HIIT. HIIT obese mice had reduced lung tumor burden compared to controls following MT challenge, and had diminished hepatic lipid deposition despite minimal body weight loss. Our findings demonstrate that HIIT can benefit obese individuals by enhancing NK cell number and activity, reducing tumor burden, and enhancing metabolic health. PMID:29302585

Prospective associations between physical activity and obesity among adolescent girls: racial differences and implications for prevention.

PubMed

White, James; Jago, Russell

2012-06-01

To test for differences in prospective associations between physical activity and obesity among black and white adolescent girls. Prospective cohort study using data from the National Heart, Lung, and Blood Institute Growth and Health Study. SETTING Multicenter study at the University of California (Berkeley), Children's Medical Center at the University of Cincinnati (Cincinnati, Ohio), and Westat, Inc, and Group Health Association (Rockville, Maryland). A total of 1148 adolescent girls (538 black and 610 white) who provided valid data on levels of physical activity and obesity at ages 12 and 14 years. Physical activity, assessed as accelerometer counts per day. Three measurements of obesity were obtained using the Centers for Disease Control and Prevention definition of obesity (at or above the age-specific 95th percentile of body mass index), the International Obesity Task Force reference body mass index cut points for obesity in children, and the sums of skinfold thickness (with the cohort ≥90th percentile as indicative of obesity). We found a strong negative dose-response association between quartiles of accelerometer counts per day at age 12 years and obesity at age 14 years (using all 3 measurements of obesity) in white but not black girls (P < .001 for body mass index interaction and P = .06 for sums of skinfold thickness interaction). The odds ratios for obesity (using the cohort ≥90th percentile for sums of skinfold thickness) in adjusted models between the top and the bottom quartiles of accelerometer counts per day were 0.15 (95% CI, 0.04-0.63; P = .03 for trend) in white girls and 0.85 (95% CI, 0.32-2.26; P = .93 for trend) in black girls. Higher levels of physical activity are prospectively associated with lower levels of obesity in white adolescent girls but not in black adolescent girls. Obesity prevention interventions may need to be adapted to account for the finding that black girls are less sensitive to the effects of physical activity.

Weighing It up: Thinking about the Implications of School Based Obesity Prevention Initiatives

ERIC Educational Resources Information Center

Leahy, Deana; Harrison, Lyn

2008-01-01

In this paper we explore the tensions that exist between two health promotion discourses prevalent in school based Health Education. We use one example from a widely used curriculum resource and one classroom episode to explore discourses related to obesity prevention, often described as an obesity epidemic by media and health professionals alike.…

The effects of incretins on energy homeostasis: physiology and implications for the treatment of type 2 diabetes mellitus and obesity.

PubMed

Karras, Spyridon; Goulis, Dimitrios G; Mintziori, Gesthimani; Katsiki, Niki; Tzotzas, Themistoklis

2012-11-01

Energy homeostasis in mammalians is a teleological process regulated by the interplay between caloric intake and energy expenditure. Incretins are a significant component of the complex homeostatic network regulating the metabolic state in humans. This narrative review will focus on the basic concepts regarding incretins physiology and their regulatory feedback mechanisms affecting energy homeostasis. In this context, glucagon-like peptide 1 (GLP-1) promotes satiety and weight loss through centrally and peripherally mediated pathways. On the other hand, gastric inhibitory peptide (GIP) is implicated in energy storage by its actions on adipose tissue. Understanding this biological model requires a holistic approach, since it is dually manifested by promoting weight reduction, in the case of GLP-1, or favoring lipid accumulation, in the case of GIP. The complete spectrum of incretin actions related to energy homeostasis is yet to be fully elucidated. Currently, new drugs based on incretin physiology are available for treatment of type 2 diabetes mellitus, whereas the implication of similar drugs in the treatment of obesity is under investigation. These agents exert several beneficial effects that minimize cardiovascular risk.

Physical activity and body functionality: implications for obesity prevention and treatment.

PubMed

Tremblay, Angelo; Therrien, Fanny

2006-02-01

Physical activity promotes metabolic adaptations that improve body functionality and contribute to the prevention of some diseases. With respect to energy and fat balance, physical activity facilitates the equilibrium between energy intake and expenditure as well as between fat intake and fat oxidation. When combined with a healthy diet that favors satiety with a reduced energy intake, exercise can induce a substantial mass loss in obese individuals. However, even the impact of an exemplary lifestyle does not seem to have the potential to decrease body mass in obese individuals down to the mass range of lean people. Up to now, we have not been able to induce mass changes exceeding 12%-15% initial body mass in obese male subjects under tolerable exercise and dietary habits, and this moderate success was accompanied by modifications in appetite and energy expenditure susceptible to compromise subsequent mass stability. As described in this paper, many environmental factors can influence energy balance and the ability to lose body fat in response to a healthy diet and (or) physical activity program. Particular attention is given to preliminary data obtained in our laboratory that suggest that knowledge-based work does not favor the same potential mass reducing effects as physical work. In fact, the acute effects of knowledge-based work suggest that this work modality may be rather susceptible to promote a more pronounced positive energy balance compared with what we may expect from a sedentary relaxing activity. This is problematic for obesity prevention in the future since knowledge-based work now represents the main working modality in a context of modernity.

The role of physical activity to control obesity problem in Malaysia

NASA Astrophysics Data System (ADS)

Abidin, Norhaslinda Zainal; Zaibidi, Nerda Zura; Zulkepli, Jafri Hj

2014-07-01

Obesity is defined as a condition in which an individual has an excess of body fat and it is accumulated to the extent that it can lead to numerous health problems and decreases the quality and length of life. Overall, the contributing factor to obesity varies. Lack of physical activity and increased sedentary behaviour has been identified as the causes of weight gain and various health implications including obesity. Rapid development in industrialization and urbanization has brought Malaysia to be the next millennium country in the world, and this causes changes in the country's socioeconomic, especially the lifestyles of Malaysians. In conjunction with this, the aim of this paper is to simulate the changes in physical activities and to highlight its implication on body weight and prevalence of overweight and obesity in a Malaysian adult population. This study combines different strands of knowledge consisting of nutrition, physical activity and body metabolism, and these elements have been synthesised into a system dynamics model called SIMULObese. The development of this model has considered the interrelations between those various strands in one multifaceted human weight regulation system. Findings from this study revealed that Malaysian adults perform less physical activity and this has resulted in weight gain and increase in prevalence of overweight and obesity. Therefore, findings from this study bring the important message to various parties such as practitioners, researchers, educators and publics about the importance of focusing on combinations of intensity, frequency and duration of moderate-vigorous activity for adult obesity control in Malaysia.

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model.

PubMed

Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann

2016-06-07

Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/-mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/-mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/-mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/-mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/-mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer.

Metabolic thrift and the genetic basis of human obesity

PubMed Central

O’Rourke, Robert W.

2014-01-01

Evolution has molded metabolic thrift within humans, a genetic heritage that, when thrust into our modern “obesogenic” environment, creates the current obesity crisis. Modern genetic analysis has identified genetic and epigenetic contributors to obesity, an understanding of which will guide the development of environmental, pharmacologic, and genetic therapeutic interventions. “The voyage was so long, food and water ran out. One hundred of the paddlers died; forty men remained. The voyagers finally reached Fitinui, then Aotona.”-From “The Story of Aka”, in The Native Culture in the Marquesas by E. S. Craighill Handy PMID:24368636

Gastro-esophageal reflux disease and obesity, where is the link?

PubMed

Emerenziani, Sara; Rescio, Maria Paola; Guarino, Michele Pier Luca; Cicala, Michele

2013-10-21

The confluence between the increased prevalence of gastro-esophageal reflux disease (GERD) and of obesity has generated great interest in the association between these two conditions. Several studies have addressed the potential relationship between GERD and obesity, but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined. A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter, thus exposing the esophageal mucosal to gastric content. Apart from the mechanical pressure, visceral fat is metabolically active and it has been strongly associated with serum levels of adipo-cytokines including interleukin-6 and tumor necrosis factor α, which may play a role in GERD or consequent carcinogenesis. This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity, and to better understand the possible role of weight loss as a therapeutic approach for GERD.

Obesity, Battle of the Bulge-Policy behind Change: Whose Responsibility Is It and Who Pays?

ERIC Educational Resources Information Center

Mercer, Adrienne

2010-01-01

Objectives: Examination of the prevalence of obesity and overweight over the past two decades and the health implications that encompass increased risk for cardiovascular disease, hypertension and diabetes. Focus on legislative policies and individual responsibility. Method: Literature review of local and national data on obesity, health…

Prenatal programming of childhood overweight and obesity.

PubMed

Huang, Jennifer S; Lee, Tiffany A; Lu, Michael C

2007-09-01

To review the scientific evidence for prenatal programming of childhood overweight and obesity, and discuss its implications for MCH research, practice, and policy. A systematic review of observational studies examining the relationship between prenatal exposures and childhood overweight and obesity was conducted using MOOSE guidelines. The review included literature posted on PubMed and MDConsult and published between January 1975 and December 2005. Prenatal exposures to maternal diabetes, malnutrition, and cigarette smoking were examined, and primary study outcome was childhood overweight or obesity as measured by body mass index (BMI) for children ages 5 to 21. Four of six included studies of prenatal exposure to maternal diabetes found higher prevalence of childhood overweight or obesity among offspring of diabetic mothers, with the highest quality study reporting an odds ratio of adolescent overweight of 1.4 (95% CI 1.0-1.9). The Dutch famine study found that exposure to maternal malnutrition in early, but not late, gestation was associated with increased odds of childhood obesity (OR 1.9, 95% CI 1.5-2.4). All eight included studies of prenatal exposure to maternal smoking showed significantly increased odds of childhood overweight and obesity, with most odds ratios clustering around 1.5 to 2.0. The biological mechanisms mediating these relationships are unknown but may be partially related to programming of insulin, leptin, and glucocorticoid resistance in utero. Our review supports prenatal programming of childhood overweight and obesity. MCH research, practice, and policy need to consider the prenatal period a window of opportunity for obesity prevention.

Ethical Issues for Public Health Approaches to Obesity.

PubMed

Azevedo, Suzanna M; Vartanian, Lenny R

2015-09-01

Obesity is a major public health concern worldwide. Because individual-level interventions have been unsuccessful at curbing obesity rates, there is an emphasis on public health approaches. In addition to testing the effectiveness of any public health interventions, it is important to consider the ethical implications of these interventions in order to protect the public's rights and promote overall well-being. In this paper, we review public health approaches to obesity in three broad domains (changes to the socio-communicative environment, changes to the economic environment, and changes to the physical environment/access) and consider the potential ethical issues that arise in each of those domains. We suggest that interventions that target the physical environment/access (making it easier for people to engage in healthy behaviors), that target the entire population (rather than just individuals with obesity), and that focus on health behaviors (rather than on weight) have the least potential for ethical concerns.

Therapeutic touch and postoperative pain: a Rogerian research study.

PubMed

Meehan, T C

1993-01-01

This article details Meehan's research study concerning the conceptualization of therapeutic touch within Rogers' science of unitary human beings and an investigation of the effects of therapeutic touch on pain experience in postoperative patients. Using a single trial, single-blind, three-group design, 108 postoperative patients were randomly assigned to receive one of the following: therapeutic touch, a placebo control intervention which mimicked therapeutic touch, or the standard intervention of a narcotic analgesic. Using a visual analogue scale, pain was measured before and one hour following intervention. The hypothesis, that therapeutic touch would significantly decrease postoperative pain compared to the placebo control intervention, was not supported. Secondary analyses suggest that therapeutic touch may decrease patients' need for analgesic medication. Implications for further research and practice are suggested.

Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics

PubMed Central

Marrache, Sean; Dhar, Shanta

2012-01-01

Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric nanoparticle (NP) system and its optimization for efficient delivery of various mitochondria-acting therapeutics by blending a targeted poly(d,l-lactic-co-glycolic acid)-block (PLGA-b)-poly(ethylene glycol) (PEG)-triphenylphosphonium (TPP) polymer (PLGA-b-PEG-TPP) with either nontargeted PLGA-b-PEG-OH or PLGA-COOH. An optimized formulation was identified through in vitro screening of a library of charge- and size-varied NPs, and mitochondrial uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with blended NPs composed of PLGA-b-PEG-TPP and a triblock copolymer containing a fluorescent quantum dot, PLGA-b-PEG-QD. The versatility of this platform was demonstrated by studying various mitochondria-acting therapeutics for different applications, including the mitochondria-targeting chemotherapeutics lonidamine and α-tocopheryl succinate for cancer, the mitochondrial antioxidant curcumin for Alzheimer’s disease, and the mitochondrial uncoupler 2,4-dinitrophenol for obesity. These biomolecules were loaded into blended NPs with high loading efficiencies. Considering efficacy, the targeted PLGA-b-PEG-TPP NP provides a remarkable improvement in the drug therapeutic index for cancer, Alzheimer’s disease, and obesity compared with the nontargeted construct or the therapeutics in their free form. This work represents the potential of a single, programmable NP platform for the diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction-related diseases. PMID:22991470

Considerations for an Obesity Policy Research Agenda

PubMed Central

McKinnon, Robin A.; Orleans, C. Tracy; Kumanyika, Shiriki K.; Haire-Joshu, Debra; Krebs-Smith, Susan M.; Finkelstein, Eric A.; Brownell, Kelly D.; Thompson, Joseph W.; Ballard-Barbash, Rachel

2010-01-01

The rise in obesity levels in the U.S. in the past several decades has been dramatic, with serious implications for public health and the economy. Experiences in tobacco control and other public health initiatives have shown that public policy may be a powerful tool to effect structural change to alter population-level behavior. In 2007, the National Cancer Institute convened a meeting to discuss priorities for a research agenda to inform obesity policy. Issues considered were how to define obesity policy research, key challenges and key partners in formulating/implementing an obesity policy research agenda, criteria by which to set research priorities, and specific research needs and questions. Themes that emerged were: (1) the embryonic nature of obesity policy research, (2) the need to study “natural experiments” resulting from policy-based efforts to address the obesity epidemic, (3) the importance of research focused beyond individual-level behavior change, (4) the need for economic research across several relevant policy areas, and (5) the overall urgency of taking action in the policy arena. Moving forward, timely evaluation of natural experiments is of especially high priority. A variety of policies intended to promote healthy weight in children and adults are being implemented in communities and at the state and national levels. Although some of these policies are supported by the findings of intervention research, additional research is needed to evaluate the implementation and quantify the impact of new policies designed to address obesity. PMID:19211215

Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity.

PubMed

Boughton, C K; Murphy, K G

2013-12-01

Obesity is a major worldwide public health issue. The physiological systems that regulate body weight are thus of great interest as targets for anti-obesity agents. Peptidergic systems are critical to the regulation of energy homeostasis by key regions in the hypothalamus and brainstem. A number of neuropeptide systems have therefore been investigated as potential treatments for obesity. Blocking orexigenic peptide signals such as neuropeptide Y, melanin-concentrating hormone, orexins, relaxin-3 and galanin-like peptide or stimulating anorectic signalling pathways used by peptides such as the melanocortins, ciliary neurotrophic factor and brain-derived neurotrophic factor, are approaches that have shown some promise, but which have also highlighted possible concerns. Manipulation of central peptidergic systems poses a number of therapeutic problems, including brain access and side effects. Given that the homeostatic defence of body weight may limit the effectiveness of any single-target therapy developed, a combination therapy approach may offer the best hope for the effective prevention and treatment of obesity. This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

The emerging role of obesity, diet and lipid metabolism in prostate cancer.

PubMed

Ferro, Matteo; Terracciano, Daniela; Buonerba, Carlo; Lucarelli, Giuseppe; Bottero, Danilo; Perdonà, Sisto; Autorino, Riccardo; Serino, Alessandro; Cantiello, Francesco; Damiano, Rocco; Andras, Iulia; De Placido, Sabino; Di Lorenzo, Giuseppe; Battaglia, Michele; Jereczek-Fossa, Barbara A; Mirone, Vincenzo; De Cobelli, Ottavio

2017-02-01

Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

Necroptosis: Modules and molecular switches with therapeutic implications.

PubMed

Arora, Deepika; Sharma, Pradeep Kumar; Siddiqui, Mohammed Haris; Shukla, Yogeshwer

2017-06-01

Among the various programmed cell death (PCD) pathways, "Necroptosis" has gained much importance as a novel paradigm of cell death. This pathway has emerged as a backup mechanism when physiologically conserved PCD (apoptosis) is non-functional either genetically or pathogenically. The expanding spectrum of necroptosis from physiological development to diverse patho-physiological disorders, including xenobiotics-mediated toxicity has now grabbed the attention worldwide. The efficient role of necroptosis regulators in disease development and management are under constant examination. In fact, few regulators (e.g. MLKL) have already paved their way towards clinical trials and others are in queue. In this review, emphasis has been paid to the various contributing factors and molecular switches that can regulate necroptosis. Here we linked the overview of current knowledge of this enigmatic signaling with magnitude of therapeutics that may underpin the opportunities for novel therapeutic approaches to suppress the pathogenesis of necroptosis-driven disorders. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults ▿

PubMed Central

Cook, Aaron M.; Martin, Craig; Adams, Val R.; Morehead, R. Scott

2011-01-01

The physiochemical properties of levofloxacin suggest that it is an agent which may exhibit altered pharmacokinetics in obese individuals. The purpose of this study was to describe the pharmacokinetics of a single 750-mg intravenous dose of levofloxacin in both hospitalized and ambulatory obese individuals. The hypothesis was that a standard dose of levofloxacin in obese individuals would achieve serum concentrations likely to be therapeutic. A single levofloxacin dose of 750 mg was infused over 90 min, and seven serial serum samples were subsequently obtained to evaluate the pharmacokinetics after the first dose. The peak concentrations of levofloxacin were comparable to those seen with normal-weight individuals. However, the area under the concentration-time curve and clearance were quite variable. Accelerated clearance was evident in the ambulatory obese individuals. Further investigation of the effects of obesity on the pharmacokinetics of levofloxacin is necessary to ensure optimal dosing. PMID:21576432

The effect of obesity, weight gain, and weight loss on asthma inception and control.

PubMed

Forno, Erick; Celedón, Juan C

2017-04-01

There is ample and growing evidence that obesity increases the risk of asthma and morbidity from asthma. Here, we review recent clinical evidence supporting a causal link between obesity and asthma, and the mechanisms that may lead to 'obese asthma'. Although in some children obesity and asthma simply co-occur, those with 'obese asthma' have increased asthma severity, lower quality of life, and reduced medication response. Underlying mechanistic pathways may include anatomical changes of the airways such as obstruction and dysanapsis, systemic inflammation, production of adipokines, impaired glucose-insulin metabolism, altered nutrient levels, genetic and epigenetic changes, and alterations in the airway and/or gut microbiome. A few small studies have shown that weight loss interventions may lead to improvements in asthma outcomes, but thus far research on therapeutic interventions for these children has been limited. Obesity increases the risk of asthma - and worsens asthma severity or control - via multiple mechanisms. 'Obese asthma' is a complex, multifactorial phenotype in children. Obesity and its complications must be managed as part of the treatment of asthma in obese children.

Drug treatment of obesity: current status and future prospects.

PubMed

Kakkar, Ashish Kumar; Dahiya, Neha

2015-03-01

Obesity is a growing epidemic and a major contributor to the global burden of disease. Obesity strains the healthcare systems and has profound economic and psychosocial consequences. Historically, pharmacotherapy for obesity has witnessed the rise and fall of several promising drug candidates that had to be eventually withdrawn due to unacceptable safety concerns. Currently four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release and naltrexone/bupropion extended release. While lorcaserin and phentermine/topiramate were approved by US Food and Drug Administration (FDA) in 2012, after a gap of 13 years following the licensing of orlistat, naltrexone/bupropion has been recently approved in 2014. This review provides a brief overview of these current therapeutic interventions available for management of obesity along with the evidence of their safety and efficacy. Additionally, several novel monotherapies as well as combination products are undergoing evaluation in various stages of clinical development. These therapies if proven successful will strengthen the existing armamentarium of antiobesity drugs and will be critical to combat the global public health crisis of obesity and its associated co-morbidities. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

The Role of Chromosomal Instability in Cancer and Therapeutic Responses

PubMed Central

Vargas-Rondón, Natalia

2017-01-01

Cancer is one of the leading causes of death, and despite increased research in recent years, control of advanced-stage disease and optimal therapeutic responses remain elusive. Recent technological improvements have increased our understanding of human cancer as a heterogeneous disease. For instance, four hallmarks of cancer have recently been included, which in addition to being involved in cancer development, could be involved in therapeutic responses and resistance. One of these hallmarks is chromosome instability (CIN), a source of genetic variation in either altered chromosome number or structure. CIN has become a hot topic in recent years, not only for its implications in cancer diagnostics and prognostics, but also for its role in therapeutic responses. Chromosomal alterations are mainly used to determine genetic heterogeneity in tumors, but CIN could also reveal treatment efficacy, as many therapies are based on increasing CIN, which causes aberrant cells to undergo apoptosis. However, it should be noted that contradictory findings on the implications of CIN for the therapeutic response have been reported, with some studies associating high CIN with a better therapeutic response and others associating it with therapeutic resistance. Considering these observations, it is necessary to increase our understanding of the role CIN plays not only in tumor development, but also in therapeutic responses. This review focuses on recent studies that suggest possible mechanisms and consequences of CIN in different disease types, with a primary focus on cancer outcomes and therapeutic responses. PMID:29283387

Childhood obesity policy: implications for African American girls and a nursing ecological model.

PubMed

Reed, Monique

2013-01-01

In the United States there is a prevalence of obesity among ethnic groups, especially African American girls. The author in this column examines through an ecological lens selected American federal, state, and city policies and program interventions aimed at reducing obesity. Specifically, the eating behavior of African American girls is discussed as a population subset for which significant gaps are present in current obesity policy and implementation. Policy recommendations should include parents as research has shown a significant relationship in the eating behaviors of African American girls and their parents. Opportunities for nurses in practice and research to test the effectiveness of family and community level policy and program initiatives that address the ecological perspectives of the adolescent environment are discussed.

Challenging Obesity: Patient, Provider, and Expert Perspectives on the Roles of Available and Emerging Nonsurgical Therapies

PubMed Central

Apovian, Caroline M.; Garvey, W. Timothy; Ryan, Donna H.

2015-01-01

Objective Adult obesity is recognized as a chronic disease. According to principles of chronic disease management, healthcare professionals should work collaboratively with patients to determine appropriate therapeutic strategies that address overweight and obesity, specifically considering a patient’s disease status in addition to their individual needs, preferences, and attitudes regarding treatment. A central role and responsibility of healthcare professionals in this process is to inform and educate patients about their treatment options. Although current recommendations for the management of adult obesity provide general guidance regarding safe and proper implementation of lifestyle, pharmacological, and surgical interventions, healthcare professionals need awareness of specific evidence-based information that supports individualized clinical application of these therapies. More specifically, healthcare professionals should be up-to-date on approaches that promote successful lifestyle management and be knowledgeable about newer weight loss pharmacotherapies, so they can offer patients with obesity a wide range of options to personalize their treatment. Accordingly, this educational activity has been developed to provide participants with the latest information on treatment recommendations and therapeutic advances in lifestyle intervention and pharmacotherapy for adult obesity management. Design and Methods This supplement is based on the content presented at a live CME symposium held in conjunction with ObesityWeek 2014. Results This supplement provides an expert summary of current treatment recommendations and recent advances in nonsurgical therapies for the management of adult obesity. Patient and provider perspectives on obesity management are highlighted in embedded video clips available via QR codes, and new evidence will be applied using clinically relevant case studies. Conclusions This supplement provides a topical update of obesity management

FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity.

PubMed

Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

2018-06-01

Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice. Male wild-type (WT) and FNDC5 -/- mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5 -/- mice. FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5 -/- mice. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing

Do diabetes and obesity affect the metabolic response to exercise?

PubMed

Plomgaard, Peter; Weigert, Cora

2017-07-01

Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice.

PubMed

Shin, Eunju; Shin, Seulmee; Kong, Hyunseok; Lee, Sungwon; Do, Seon-Gil; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil; Hwang, In-Kyeong; Kim, Kyungjae

2011-04-01

Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Aloe QDM complex down-regulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1β and -6) and HIF1α mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-κB p65 from the cytosol in the WAT. Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice

PubMed Central

Shin, Eunju; Shin, Seulmee; Kong, Hyunseok; Lee, Sungwon; Do, Seon-Gil; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil; Hwang, In-Kyeong

2011-01-01

Background Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results Aloe QDM complex down-regulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1β and -6) and HIF1α mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-κB p65 from the cytosol in the WAT. Conclusion Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation. PMID:21637388

Breastfeeding Reduces Childhood Obesity Risks.

PubMed

Wang, Liang; Collins, Candice; Ratliff, Melanie; Xie, Bin; Wang, Youfa

2017-06-01

The present study examined the effects of breastfeeding and its duration on the development of childhood obesity from 24 months through grade 6. U.S. longitudinal data collected from 1234 children were analyzed using logistic regression models and generalized estimating equation (GEE). Child height and weight were measured six times at ages of 24 months, 36 months, 54 months, grade 1, grade 3, and grade 6. During the early 1990s, prevalence of breastfeeding was low in the United States, 60% and 48% at 1 and 6 months, respectively. Nonsmoking, white, married mothers with both parents in the household, and with income above the poverty line, were more likely to breastfeed at 1 month of age of their babies. Obesity rate of the children increased with age from 24 months to grade 6. Logistic regression showed that breastfeeding at month 1 was associated with 53% (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.30-0.73) and 47% (OR: 0.53, 95% CI: 0.36-0.78) decreased risks for childhood obesity at grades 1 and 6, respectively. GEE analysis showed that breastfeeding at 1 month reduced risk for childhood obesity by 36% (95% CI: 0.47-0.88) from ages 24 months through grade 6. Regarding breastfeeding duration, more than 6 months (vs. never) was associated with a decreased risk for childhood obesity by 42% (OR: 0.58, 95% CI: 0.36-0.94). Breastfeeding at 1 month and more than 6 months reduced the risk of childhood obesity. Rate of breastfeeding was low in the United States in the 1990s, which may have had long-term implications on children.

The Whitening of Brown Fat and Its Implications for Weight Management in Obesity.

PubMed

Shimizu, Ippei; Walsh, Kenneth

2015-06-01

Systemic inflammation resulting from dysfunction of white adipose tissue (WAT) accelerates the pathologies of diabetes and cardiovascular diseases. In contrast to WAT, brown adipose tissue (BAT) is abundant in mitochondria that produce heat by uncoupling respiratory chain process of ATP synthesis. Besides BAT's role in thermogenesis, accumulating evidence has shown that it is involved in regulating systemic metabolism. Studies have analyzed the "browning" processes of WAT as a means to combat obesity, whereas few studies have focused on the impact and molecular mechanisms that contribute to obesity-linked BAT dysfunction--a process that is associated with the "whitening" of this tissue. Compared to WAT, a dense vascular network is required to support the high energy consumption of BAT. Recently, vascular rarefaction was shown to be a significant causal factor in the whitening of BAT in mouse models. Vascular insufficiency leads to mitochondrial dysfunction and loss in BAT and contributes to systemic insulin resistance. These data suggest that BAT "whitening," resulting from vascular dysfunction, can impact obesity and obesity-linked diseases. Conversely, agents that promote BAT function could have utility in the treatment of these conditions.

Exploring occupational and health behavioral causes of firefighter obesity: a qualitative study.

PubMed

Dobson, Marnie; Choi, BongKyoo; Schnall, Peter L; Wigger, Erin; Garcia-Rivas, Javier; Israel, Leslie; Baker, Dean B

2013-07-01

Firefighters, as an occupational group, have one of the highest prevalence rates of obesity. A qualitative study investigated occupational and health behavioral determinants of obesity among firefighters. Four focus groups were conducted with firefighters of every rank as Phase I of the FORWARD study which was designed to assess health behavioral and occupational characteristics related to obesity in firefighters. Analysis revealed five main themes of central importance to firefighters: (1) fire station eating culture; (2) night calls and sleep interruption; (3) supervisor leadership and physical fitness; (4) sedentary work; and (5) age and generational influences. The results showed a strong interrelationship between occupational and health behavioral causes of obesity in firefighters. The relevance of these qualitative findings are discussed along with the implications for future obesity interventions with firefighters. Copyright © 2013 Wiley Periodicals, Inc.

Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review.

PubMed

Dahiya, Dinesh K; Renuka; Puniya, Monica; Shandilya, Umesh K; Dhewa, Tejpal; Kumar, Nikhil; Kumar, Sanjeev; Puniya, Anil K; Shukla, Pratyoosh

2017-01-01

In the present world scenario, obesity has almost attained the level of a pandemic and is progressing at a rapid rate. This disease is the mother of all other metabolic disorders, which apart from placing an added financial burden on the concerned patient also has a negative impact on his/her well-being and health in the society. Among the various plausible factors for the development of obesity, the role of gut microbiota is very crucial. In general, the gut of an individual is inhabited by trillions of microbes that play a significant role in host energy homeostasis by their symbiotic interactions. Dysbiosis in gut microbiota causes disequilibrium in energy homeostasis that ultimately leads to obesity. Numerous mechanisms have been reported by which gut microbiota induces obesity in experimental models. However, which microbial community is directly linked to obesity is still unknown due to the complex nature of gut microbiota. Prebiotics and probiotics are the safer and effective dietary substances available, which can therapeutically alter the gut microbiota of the host. In this review, an effort was made to discuss the current mechanisms through which gut microbiota interacts with host energy metabolism in the context of obesity. Further, the therapeutic approaches (prebiotics/probiotics) that helped in positively altering the gut microbiota were discussed by taking experimental evidence from animal and human studies. In the closing statement, the challenges and future tasks within the field were discussed.

Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review

PubMed Central

Dahiya, Dinesh K.; Renuka; Puniya, Monica; Shandilya, Umesh K.; Dhewa, Tejpal; Kumar, Nikhil; Kumar, Sanjeev; Puniya, Anil K.; Shukla, Pratyoosh

2017-01-01

In the present world scenario, obesity has almost attained the level of a pandemic and is progressing at a rapid rate. This disease is the mother of all other metabolic disorders, which apart from placing an added financial burden on the concerned patient also has a negative impact on his/her well-being and health in the society. Among the various plausible factors for the development of obesity, the role of gut microbiota is very crucial. In general, the gut of an individual is inhabited by trillions of microbes that play a significant role in host energy homeostasis by their symbiotic interactions. Dysbiosis in gut microbiota causes disequilibrium in energy homeostasis that ultimately leads to obesity. Numerous mechanisms have been reported by which gut microbiota induces obesity in experimental models. However, which microbial community is directly linked to obesity is still unknown due to the complex nature of gut microbiota. Prebiotics and probiotics are the safer and effective dietary substances available, which can therapeutically alter the gut microbiota of the host. In this review, an effort was made to discuss the current mechanisms through which gut microbiota interacts with host energy metabolism in the context of obesity. Further, the therapeutic approaches (prebiotics/probiotics) that helped in positively altering the gut microbiota were discussed by taking experimental evidence from animal and human studies. In the closing statement, the challenges and future tasks within the field were discussed. PMID:28421057

[EARLY MOTHER-CHILD BONDING FACTORS ASSOCIATED WITH CHILDREN OBESITY].

PubMed

Vargas Martínez, Gabriela; Cruzat Mandich, Claudia; Díaz Castrillón, Fernanda; Moore Infante, Catalina; Ulloa Jiménez, Valentina

2015-11-01

The aim of this study is to describe the experience of a group of mothers with obese children, regarding how early bond affects the relationship that both have with food and this, in turn, impacts on childhood obesity. The present study has a qualitative, exploratory and descriptive design. The sample consists of five chilean women between 22 and 39 years old, with obese children between 2 and 4 years old. In-depth interviews were carried out and open coding strategy was used as method of analysis. Results show a tendency of mothers to establish insecure attachment relations, difficulties of tuning and expression of affection, and a predominance of a permissive parenting style around food. This has important implications for prevention and treatment of obesity, focusing on the attachment bond between mother and child. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

PubMed

Saad, M J A; Santos, A; Prada, P O

2016-07-01

Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

Putative Effects of Obesity on Linear Growth and Puberty
.

PubMed

Shalitin, Shlomit; Kiess, Wieland

2017-01-01

Childhood obesity is a major public health problem that has grown to epidemic proportions throughout the world. Obesity is influenced by genetic and environmental factors. The nutritional status plays an important role in growth and body weight regulation. Excess adiposity during childhood can affect the process of growth and puberty. Obese children are frequently tall for their age, with accelerated epiphyseal growth plate maturation despite low growth hormone levels. Several regulatory hormones may affect the process of linear growth in the constellation of obesity, as high levels of insulin and leptin are observed in obese children. Leptin can act as a skeletal growth factor, with a direct effect on skeletal growth centers. The finding that overweight children, especially girls, tend to mature earlier than lean children has led to the hypothesis that the degree of body fatness may trigger the neuroendocrine events that lead to the onset of puberty. Leptin receptors have been identified in the hypothalamus, as well as in gonadotrope cells, ovarian follicular cells, and Leydig cells. The increased leptin and androgen levels seen in obese children may be implicated in their earlier onset of puberty and accelerated pubertal growth. This review is focused on the interaction between childhood obesity and growth and pubertal processes.
. © 2017 S. Karger AG, Basel.

Gut Microbiota: From Microorganisms to Metabolic Organ Influencing Obesity.

PubMed

Stephens, Richard W; Arhire, Lidia; Covasa, Mihai

2018-05-01

This review summarizes the current understanding of the relationship between gut microbiota and the host as it pertains to the regulation of energy balance and obesity. The paper begins with a brief description of the gut microbiota environment, distribution, and its unique symbiotic relationship with the host. The way that enviromental factors influence microbiota composition and subsequent impact on the host are then described. Next, the mechanisms linking gut dysbiosis with obesity are discussed, and finally current challenges and limitations in understanding the role of gut microbiota in control of obesity are presented. Gut microbiota has been implicated in regulation of fat storage, as well as gut dysbiosis, thus contributing to the development of obesity, insulin resistance, hyperglycemia and hyperlipidemia. However, the underlying mechanisms of these processes are far from being clear and will require complex preclinical and clinical interdisciplinary studies of bacteria and host cell-to-cell interactions. There is a need for a better understanding of how changes in gut microbiota composition can impact energy balance and thus control weight gain. This may represent a promising avenue in the race to develop nonsurgical treatments for obesity. © 2018 The Obesity Society.

Medical Student Bias and Care Recommendations for an Obese versus Non-Obese Virtual Patient

PubMed Central

Persky, Susan; Eccleston, Collette P.

2010-01-01

Objective This study examined the independent effect of a patient's weight on medical students' attitudes, beliefs, and interpersonal behavior toward the patient, in addition to the clinical recommendations they make for her care. Design Seventy-six clinical-level medical students were randomly assigned to interact with a digital, virtual female patient who was visibly either obese or non-obese. Methods Interactions with the patient took place in an immersive virtual clinical environment (i.e., virtual reality) which allowed standardization of all patient behaviors and characteristics except for weight. Visual contact behavior was automatically recorded during the interaction. Afterward, participants filled out a battery of self-report questionnaires. Results Analyses revealed more negative stereotyping, less anticipated patient adherence, worse perceived health, more responsibility attributed for potentially weight-related presenting complaints, and less visual contact directed toward the obese version of a virtual patient than the non-obese version of the patient. In contrast, there was no clear evidence of bias in clinical recommendations made for the patient's care. Conclusion Biases in attitudes, beliefs, and interpersonal behavior have important implications because they can influence the tone of clinical encounters and rapport in the patient-provider relationship, which can have important downstream consequences. Gaining a clear understanding of the nature and source of weight bias in the clinical encounter is an important first step toward development of strategies to address it. PMID:20820169

Mini-review: Obesity in Caribbean Youth.

PubMed

Traboulay, E A; Hoyte, O P-A

2015-06-01

Our focus was on the determination of the growing number of youths of every race and ethnicity, diagnosed with obesity and its co-morbidities in the Caribbean. We reviewed the causes and strategies to combat obesity, and the implications of the fast food industry in enabling the escalation of obesity. We consulted several databases such as PubMed, MEDLINE, the Obesity Gene Map Database, and the USEPA Toxicity Reference Database. Organizations such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), Organization for Economic Co-operation and Development (OECD) and the Pan American Health Organization (PAHO) were used as information sources. Transgenerational effects and triggers like obesogens, pathogens, environmental stress, antibiotics and gut microbiota are some of the causes of obesity, and some of these triggers are imprinted epigenetically early in embryonic development, leading to lifelong obesity. With an estimated population of 42 million in the Caribbean, the economic cost of obesity, including medical, absenteeism, presenteeism, insurance, disability, direct and indirect cost, was estimated cost of 68.5 billion USD with 88.2 million quality-adjusted life years lost. Genome-wide association studies have established that genetics play a role in the aetiology of this "non-communicable" disease. While the development of personalized interventions according to genotype is futuristic, we must focus on effective nutrition and physical education classes in schools and establishing monitoring programmes using simple tools such as scales and tape measures as suggested intervention. A Pigovian tax to control the fast food industry is mandatory. Nevertheless, lifestyle adjustment, including alterations in diet and increased physical activity, continues to be a sound recommendation.

Mini-review: Obesity in Caribbean Youth

PubMed Central

Traboulay, EA; Hoyte, OPA

2015-01-01

ABSTRACT Objective: Our focus was on the determination of the growing number of youths of every race and ethnicity, diagnosed with obesity and its co-morbidities in the Caribbean. We reviewed the causes and strategies to combat obesity, and the implications of the fast food industry in enabling the escalation of obesity. Methods: We consulted several databases such as PubMed, MEDLINE, the Obesity Gene Map Database, and the USEPA Toxicity Reference Database. Organizations such as the World Health Organization (WHO), Centres for Disease Control and Prevention (CDC), Organization for Economic Co-operation and Development (OECD), and the Pan American Health Organization (PAHO) were used as information sources. Results: Transgenerational effects and triggers like obesogens, pathogens, environmental stress, antibiotics and gut microbiota are some of the causes of obesity, and some of these triggers are imprinted epigenetically early in embryonic development, leading to lifelong obesity. With an estimated population of 42 million in the Caribbean, the economic cost of obesity, including medical, absenteeism, presenteeism, insurance, disability, direct and indirect cost, was estimated at 68.5 billion USD with 88.2 million quality-adjusted life years lost. Conclusion: Genome-wide association studies have established that genetics play a role in the aetiology of this “non-communicable” disease. While the development of personalized interventions according to genotype is futuristic, we must focus on effective nutrition and physical education (PE) classes in schools and establishing monitoring programmes using simple tools such as scales and tape measures as suggested intervention. A Pigovian tax to control the fast food industry is mandatory. Nevertheless, lifestyle adjustment, including alterations in diet and increased physical activity, continues to be a sound recommendation. PMID:26426179

Socioeconomic status, infant feeding practices and early childhood obesity.

PubMed

Gibbs, B G; Forste, R

2014-04-01

Children from low socioeconomic households are at greater risk of obesity. As breastfeeding can protect against child obesity, disadvantaged infants are less likely to breastfeed relative to more advantaged children. Whether infant feeding patterns, as well as other maternal characteristics mediate the association between social class and obesity has not been established in available research. Examine the impact of infant feeding practices on child obesity and identify the mechanisms that link socioeconomic status (SES) with child obesity. Based on a nationally representative longitudinal survey (ECLS-B) of early childhood (n = 8030), we examine how breastfeeding practices, the early introduction of solid foods and putting an infant to bed with a bottle mediate the relationship between social class and early childhood obesity relative to the mediating influence of other maternal characteristics (BMI, age at birth, smoking, depression and daycare use). Infants predominantly fed formula for the first 6 months were about 2.5 times more likely to be obese at 24 months of age relative to infants predominantly fed breast milk. The early introduction of solid foods (< 4 months) and putting the child to bed with a bottle also increased the likelihood of obesity. Unhealthy infant feeding practices were the primary mechanism mediating the relationship between SES and early childhood obesity. Results are consistent across measures of child obesity although the effect size of infant feeding practices varies. The encouragement and support of breastfeeding and other healthy feeding practices are especially important for low socioeconomic children who are at increased risk of early childhood obesity. Targeting socioeconomically disadvantaged mothers for breastfeeding support and for infant-led feeding strategies may reduce the negative association between SES and child obesity. The implications are discussed in terms of policy and practice. © 2013 The Authors. Pediatric

Ozone Exposure, Cardiopulmonary Health, and Obesity: A Substantive Review.

PubMed

Koman, Patricia D; Mancuso, Peter

2017-07-17

From 1999-2014, obesity prevalence increased among adults and youth. Obese individuals may be uniquely susceptible to the proinflammatory effects of ozone because obese humans and animals have been shown to experience a greater decline in lung function than normal-weight subjects. Obesity is independently associated with limitations in lung mechanics with increased ozone dose. However, few epidemiologic studies have examined the interaction between excess weight and ozone exposure among adults. Using PubMed keyword searches and reference lists, we reviewed epidemiologic evidence to identify potential response-modifying factors and determine if obese or overweight adults are at increased risk of ozone-related health effects. We initially identified 170 studies, of which seven studies met the criteria of examining the interaction of excess weight and ozone exposure on cardiopulmonary outcomes in adults, including four short-term ozone exposure studies in controlled laboratory settings and three community epidemiologic studies. In the studies identified, obesity was associated with decreased lung function and increased inflammatory mediators. Results were inconclusive about the effect modification when data were stratified by sex. Obese and overweight populations should be considered as candidate at-risk groups for epidemiologic studies of cardiopulmonary health related to air pollution exposures. Air pollution is a modifiable risk factor that may decrease lung function among obese individuals with implications for environmental and occupational health policy.

Prevention of childhood obesity: sociocultural and familial factors.

PubMed

Bruss, Mozhdeh B; Morris, Joseph; Dannison, Linda

2003-08-01

This study examined sociocultural and familial factors related to the prevention of childhood obesity. Primary caregivers of 6- to 10-year-old children representing several ethnic populations in Saipan participated in 4 focus groups (N=32). Trained moderators used semi-structured interviews and qualitative methods were used in data analysis. A central theme with several related factors emerged. The theme was a conflict expressed by the primary caregiver between sociocultural values, family expectations, traditional dietary beliefs and attitudes, and knowledge about food and disease. These findings have important implications for designing culturally sensitive interventions for prevention of childhood obesity.

Including Overweight and Obese Students in Physical Education: An Urgent Need and Effective Teaching Strategies

ERIC Educational Resources Information Center

Li, Huanyu; Li, Weidong; Zhao, Qi; Li, Mingda

2017-01-01

Students who are overweight or obese generally have low physical ability and fitness levels, experience serious weight-related health implications, are teased and excluded by their peers, and suffer psycho-social and emotional damages as a result of weight stigma. Overweight and obese students have presented an unprecedented challenge for teachers…

Prioritizing Environmental Chemicals for Obesity and Diabetes ...

EPA Pesticide Factsheets

Background: Diabetes and obesity are major threats to public health in the US and abroad. Understanding the role chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is a challenge. This review is intended to help researchers generate hypotheses about chemicals potentially contributing to diabetes and obesity-related health outcomes by summarizing relevant findings from the US Environmental Protection Agency (EPA) ToxCast high-throughput screening (HTS) program. Objectives: To develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high throughput screening data. Methods: Identify ToxCast assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and beta cell function, adipocyte dierentiation, and feeding behavior) and present chemical screening data against those assay targets to identify chemicals of potential interest. Discussion: Results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated from research papers and reviews published in the peer-reviewed literature. Testing of hypotheses based on ToxCast data will a

Educational attainment and obesity: A systematic review

PubMed Central

Cohen, Alison K.; Rai, Manisha; Rehkopf, David H.; Abrams, Barbara

2013-01-01

Background Although previous systematic reviews considered the relationship between socioeconomic status and obesity, almost 200 peer-reviewed articles have been published since the last review on that topic, and this paper focuses specifically on education, which has different implications. Methods The authors systematically review the peer-reviewed literature from around the world considering the association between educational attainment and obesity. Databases from public health and medicine, education, psychology, economics, and other social sciences were searched, and articles published in English, French, Portuguese, and Spanish were included. Results This paper includes 289 articles that report on 410 populations in 91 countries. The relationship between educational attainment and obesity was modified by both gender and the country's economic development level: an inverse association was more common in studies of higher-income countries and a positive association was more common in lower-income countries, with stronger social patterning among women. Relatively few studies reported on lower-income countries, controlled for a comprehensive set of potential confounding variables, and/or attempted to assess causality through the use of quasi-experimental designs. Conclusions Future research should address these gaps to understand if the relationship between educational attainment and obesity may be causal, thus supporting education policy as a tool for obesity prevention. PMID:23889851