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1.
Annu Rev Biochem ; 85: 5-34, 2016 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-27145842

RESUMEN

Dietary restriction (DR), a moderate reduction in food intake, improves health during aging and extends life span across multiple species. Specific nutrients, rather than overall calories, mediate the effects of DR, with protein and specific amino acids (AAs) playing a key role. Modulations of single dietary AAs affect traits including growth, reproduction, physiology, health, and longevity in animals. Epidemiological data in humans also link the quality and quantity of dietary proteins to long-term health. Intricate nutrient-sensing pathways fine tune the metabolic responses to dietary AAs in a highly conserved manner. In turn, these metabolic responses can affect the onset of insulin resistance, obesity, neurodegenerative disease, and other age-related diseases. In this review we discuss how AA requirements are shaped and how ingested AAs regulate a spectrum of homeostatic processes. Finally, we highlight the resulting opportunity to develop nutritional strategies to improve human health during aging.


Asunto(s)
Envejecimiento/genética , Aminoácidos/metabolismo , Dieta con Restricción de Proteínas/métodos , Proteínas en la Dieta/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas Serina-Treonina Quinasas/genética , Envejecimiento/metabolismo , Aminoácidos/administración & dosificación , Animales , Restricción Calórica , Proteínas en la Dieta/administración & dosificación , Factor 2 Eucariótico de Iniciación/genética , Factor 2 Eucariótico de Iniciación/metabolismo , Homeostasis/genética , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina , Complejos Multiproteicos/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/prevención & control , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , Obesidad/prevención & control , Proteínas Serina-Treonina Quinasas/metabolismo , Deficiencias en la Proteostasis/genética , Deficiencias en la Proteostasis/metabolismo , Deficiencias en la Proteostasis/patología , Deficiencias en la Proteostasis/prevención & control , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
2.
Cell ; 159(2): 306-17, 2014 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-25303527

RESUMEN

Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here, we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked ß-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates fundamental cellular processes. The levels of O-GlcNAc transferase (OGT) and O-GlcNAc modification are enriched in AgRP neurons and are elevated by fasting. Genetic ablation of OGT in AgRP neurons inhibits neuronal excitability through the voltage-dependent potassium channel, promotes white adipose tissue browning, and protects mice against diet-induced obesity and insulin resistance. These data reveal adipose tissue browning as a highly dynamic physiological process under central control, in which O-GlcNAc signaling in AgRP neurons is essential for suppressing thermogenesis to conserve energy in response to fasting.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Dieta , N-Acetilglucosaminiltransferasas/metabolismo , Neuronas/metabolismo , Tejido Adiposo Blanco/metabolismo , Proteína Relacionada con Agouti/metabolismo , Animales , Ayuno , Femenino , Ghrelina/metabolismo , Hipotálamo/citología , Hipotálamo/metabolismo , Resistencia a la Insulina , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , N-Acetilglucosaminiltransferasas/genética , Obesidad/metabolismo , Obesidad/prevención & control
3.
Nature ; 606(7915): 785-790, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35705806

RESUMEN

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.


Asunto(s)
Ingestión de Alimentos , Conducta Alimentaria , Obesidad , Fenilalanina , Condicionamiento Físico Animal , Adiposidad/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2 , Modelos Animales de Enfermedad , Ingestión de Alimentos/fisiología , Metabolismo Energético , Conducta Alimentaria/fisiología , Glucosa/metabolismo , Ácido Láctico/metabolismo , Ratones , Obesidad/metabolismo , Obesidad/prevención & control , Fenilalanina/administración & dosificación , Fenilalanina/análogos & derivados , Fenilalanina/metabolismo , Fenilalanina/farmacología , Condicionamiento Físico Animal/fisiología
4.
Cell ; 149(3): 671-83, 2012 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-22541436

RESUMEN

Obesity, type 2 diabetes, and heart failure are associated with aberrant cardiac metabolism. We show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a. Cardiac-specific overexpression of MED13 or pharmacologic inhibition of miR-208a in mice confers resistance to high-fat diet-induced obesity and improves systemic insulin sensitivity and glucose tolerance. Conversely, genetic deletion of MED13 specifically in cardiomyocytes enhances obesity in response to high-fat diet and exacerbates metabolic syndrome. The metabolic actions of MED13 result from increased energy expenditure and regulation of numerous genes involved in energy balance in the heart. These findings reveal a role of the heart in systemic metabolic control and point to MED13 and miR-208a as potential therapeutic targets for metabolic disorders.


Asunto(s)
Metabolismo Energético , Resistencia a la Insulina , MicroARNs/metabolismo , Miocardio/metabolismo , Obesidad/genética , Animales , Diabetes Mellitus Tipo 2 , Femenino , Glucosa/metabolismo , Corazón/fisiología , Homeostasis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Obesidad/prevención & control
5.
Cell ; 148(3): 421-33, 2012 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-22304913

RESUMEN

Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca(2+) levels and activates the CamKKß-AMPK pathway via phospholipase C and the ryanodine receptor Ca(2+)-release channel. As a consequence, resveratrol increases NAD(+) and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging.


Asunto(s)
3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Envejecimiento/metabolismo , Restricción Calórica , Transducción de Señal , Estilbenos/administración & dosificación , 3',5'-AMP Cíclico Fosfodiesterasas/química , 3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Tejido Adiposo Blanco/efectos de los fármacos , Animales , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/química , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Dieta , Intolerancia a la Glucosa/prevención & control , Factores de Intercambio de Guanina Nucleótido/metabolismo , Ratones , Modelos Moleculares , Músculo Esquelético/efectos de los fármacos , NAD/metabolismo , Obesidad/prevención & control , Proteínas Quinasas/metabolismo , Resveratrol , Rolipram/administración & dosificación , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Sirtuina 1/metabolismo
6.
Nature ; 600(7888): 314-318, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34819664

RESUMEN

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.


Asunto(s)
Adipocitos/metabolismo , Metabolismo Energético , Interleucina-27/metabolismo , Termogénesis , Animales , Cirugía Bariátrica , Modelos Animales de Enfermedad , Femenino , Humanos , Resistencia a la Insulina , Interleucina-27/sangre , Interleucina-27/uso terapéutico , Masculino , Ratones , Obesidad/sangre , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/prevención & control , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Receptores de Interleucina/metabolismo , Transducción de Señal , Proteína Desacopladora 1/biosíntesis , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
7.
Mol Cell ; 72(6): 985-998.e7, 2018 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-30415949

RESUMEN

Current models of SIRT1 enzymatic regulation primarily consider the effects of fluctuating levels of its co-substrate NAD+, which binds to the stably folded catalytic domain. By contrast, the roles of the sizeable disordered N- and C-terminal regions of SIRT1 are largely unexplored. Here we identify an insulin-responsive sensor in the SIRT1 N-terminal region (NTR), comprising an acidic cluster (AC) and a 3-helix bundle (3HB), controlling deacetylase activity. The allosteric assistor DBC1 removes a distal N-terminal shield from the 3-helix bundle, permitting PACS-2 to engage the acidic cluster and the transiently exposed helix 3 of the 3-helix bundle, disrupting its structure and inhibiting catalysis. The SIRT1 activator (STAC) SRT1720 binds and stabilizes the 3-helix bundle, protecting SIRT1 from inhibition by PACS-2. Identification of the SIRT1 insulin-responsive sensor and its engagement by the DBC1 and PACS-2 regulatory hub provides important insight into the roles of disordered regions in enzyme regulation and the mode by which STACs promote metabolic fitness.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Hepatocitos/enzimología , Insulina/metabolismo , Sirtuina 1/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Regulación Alostérica , Animales , Sitios de Unión , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Células HCT116 , Hepatocitos/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Resistencia a la Insulina , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/enzimología , Obesidad/genética , Obesidad/prevención & control , Unión Proteica , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Estabilidad Proteica , Sirtuina 1/genética , Proteínas de Transporte Vesicular/deficiencia , Proteínas de Transporte Vesicular/genética
8.
PLoS Biol ; 20(2): e3001517, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35202387

RESUMEN

Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight through activation of hindbrain receptor glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) in rodents and nonhuman primates, thus endogenous induction of this peptide holds promise for obesity treatment. Here, through in silico drug-screening methods, we found that small molecule Camptothecin (CPT), a previously identified drug with potential antitumor activity, is a GDF15 inducer. Oral CPT administration increases circulating GDF15 levels in diet-induced obese (DIO) mice and genetic ob/ob mice, with elevated Gdf15 expression predominantly in the liver through activation of integrated stress response. In line with GDF15's anorectic effect, CPT suppresses food intake, thereby reducing body weight, blood glucose, and hepatic fat content in obese mice. Conversely, CPT loses these beneficial effects when Gdf15 is inhibited by a neutralizing antibody or AAV8-mediated liver-specific knockdown. Similarly, CPT failed to reduce food intake and body weight in GDF15's specific receptor GFRAL-deficient mice despite high levels of GDF15. Together, these results indicate that CPT is a promising anti-obesity agent through activation of GDF15-GFRAL pathway.


Asunto(s)
Camptotecina/farmacología , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor 15 de Diferenciación de Crecimiento/genética , Obesidad/prevención & control , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/genética , Camptotecina/farmacocinética , Línea Celular , Línea Celular Tumoral , Dieta Alta en Grasa/efectos adversos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/genética , Regulación de la Expresión Génica/efectos de los fármacos , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Factor 15 de Diferenciación de Crecimiento/metabolismo , Células HEK293 , Células HL-60 , Humanos , Células MCF-7 , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Obesidad/etiología , Obesidad/genética , Células PC-3
11.
J Hepatol ; 80(4): 543-552, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38092157

RESUMEN

BACKGROUND & AIMS: Chronic liver disease (CLD) causes 1.8% of all deaths in Europe, many of them from liver cancer. We estimated the impact of several policy interventions in France, the Netherlands, and Romania. METHODS: We used a validated microsimulation model to assess seven different policy scenarios in 2022-2030: a minimum unit price (MUP) of alcohol of €0.70 or €1, a volumetric alcohol tax, a sugar-sweetened beverage (SSB) tax, food marketing restrictions, plus two different combinations of these policies compared against current policies (the 'inaction' scenario). RESULTS: All policies reduced the burden of CLD and liver cancer. The largest impact was observed for a MUP of €1, which by 2030 would reduce the cumulative incidence of CLD by between 7.1% to 7.3% in France, the Netherlands, and Romania compared with inaction. For liver cancer, the corresponding reductions in cumulative incidence were between 4.8% to 5.8%. Implementing a package containing a MUP of €0.70, a volumetric alcohol tax, and an SSB tax would reduce the cumulative incidence of CLD by between 4.29% to 4.71% and of liver cancer by between 3.47% to 3.95% in France, the Netherlands, and Romania. The total predicted reduction in healthcare costs by 2030 was greatest with the €1 MUP scenario, with a reduction for liver cancer costs of €8.18M and €612.49M in the Netherlands and France, respectively. CONCLUSIONS: Policy measures tackling primary risk factors for CLD and liver cancer, such as the implementation of a MUP of €1 and/or a MUP of €0.70 plus SSB tax could markedly reduce the number of Europeans with CLD or liver cancer. IMPACT AND IMPLICATIONS: Policymakers must be aware that alcohol and obesity are the two leading risk factors for chronic liver disease and liver cancer in Europe and both are expected to increase in the future if no policy interventions are made. This study assessed the potential of different public health policy measures to mitigate the impact of alcohol consumption and obesity on the general population in three European countries: France, the Netherlands, and Romania. The findings support introducing a €1 minimum unit price for alcohol to reduce the burden of chronic liver disease. In addition, the study shows the importance of targeting multiple drivers of alcohol consumption and obesogenic products simultaneously via a harmonized fiscal policy framework, to complement efforts being made within health systems. These findings should encourage policymakers to introduce such policy measures across Europe to reduce the burden of liver disease. The modeling methods used in this study can assist in structuring similar modeling in other regions to expand on this study's findings.


Asunto(s)
Enfermedades del Sistema Digestivo , Neoplasias Hepáticas , Humanos , Impuestos , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/prevención & control , Obesidad/epidemiología , Obesidad/prevención & control , Etanol , Políticas , Costos de la Atención en Salud , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control
12.
Lancet ; 402 Suppl 1: S9, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37997136

RESUMEN

BACKGROUND: Poor diet is a major public health concern. In 2021, 63·8% of adults and 22·2% of reception-age children were either overweight or obese in England. Fiscal interventions have become a popular policy measure to reduce obesity and encourage healthy eating. Such measures are highly controversial, leading to media debate promoting pro-tax and anti-tax arguments. To better understand food tax debates and the use of media analysis in public health research, we conducted a scoping review of media analyses using food taxes as a case study. METHODS: In this scoping review, we searched SCOPUS, PubMed, and EBSCOhost databases on Feb 14-22, 2023, using keyword variations for "food", "tax", and "media analysis". Results were restricted to English-only, peer-reviewed journal articles. The initial results were manually screened through an iterative process to exclude articles that did not analyse a food tax, were non-English language, were not peer-reviewed, or did not use media analysis as the primary method. Modelled on Arksey and O'Malley's (2005) five-stage review protocol, two researchers used a coding framework to independently code all articles and checked result quality through regular discussion. Extracted data included article title, author, year, country, tax type, media sources used, identified media frames, and research aims, methods, results, and conclusions. Results are reported according to PRISMA guidelines and data files submitted to FigShare Repository (non-accessible). FINDINGS: Of 1087 articles reviewed, 19 were eligible to be included in the study. Articles were published between 2013 and 2023, with 2021 having the highest concentration of studies carried out mainly in UK and USA. Despite search terms encompassing a range of food products, the retrieved media analyses focused on three types of food product taxes: sugar-sweetened beverages, meat, and groceries. Most articles explored arguments for and against policy implementation, with some investigating stakeholder representation. Results demonstrate that stakeholders' arguments, both positive and negative, are consistent across countries and food products. INTERPRETATION: The consistency of how both pro-tax and anti-tax arguments are presented in the media demonstrates the importance of coordination between stakeholder groups to influence policy adoption. To our knowledge, this is the first study to investigate media analysis across a diverse range of food products. FUNDING: National Institute for Health and Care Research (NIHR).


Asunto(s)
Alimentos , Salud Pública , Adulto , Niño , Humanos , Obesidad/prevención & control , Sobrepeso , Impuestos
13.
Lancet ; 402 Suppl 1: S20, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37997060

RESUMEN

BACKGROUND: Obesity epidemic is one of the greatest challenges in public health in modern societies. This study aimed to address the main gap by reviewing the effectiveness of nutritional policy measures implemented globally by governments to reduce obesity prevalence among adults. METHODS: We developed a scoping review by searching Ovid Medline, PubMed, and Embase from May 5, to July 12, 2022 for papers published in English between Jan 1, 2002 and May 1, 2022. Eligible papers included adults older than 18 years and focused on obesity prevention strategies. No restrictions on study design or geographic location were applied. The search terms included "obesity", "health policy", "government regulation", and "obesogenic environment". FINDINGS: 17 articles were eligible for this scoping review across seven countries (USA, UK, France, Mexico, Colombia, Chile, and India). The identified studies were observational, cross-sectional, and systematic reviews, with the majority published in the USA and the UK within the past 5 years. Policies were categorised into three groups: food and beverages taxes (n=6), food labelling (n=6) and national campaigns (n=5). Most policies showed a small magnitude change in obesity reduction metrics such as body-mass index (BMI) and weight outcome (n=10). Two studies found that food labelling did not significantly change weight status. Two other studies targeting national campaigns showed a reduction in risk for obesity and overweight. However, the sugar tax demonstrated promising results compared with all other policies when the tax levy tier was increased. Three studies reported that a higher tax increase was correlated with a greater decline in obesity prevalence when increasing the tax up to 20%. INTERPRETATION: Our findings inform recommendations for policy makers of how other countries have implemented and evaluated their food policies. It can also encourage food industries to reformulate their products and promote population health. The limited number of settings included in this study is a main limitation of the review. Further investigation of the tax equity is needed. FUNDING: None.


Asunto(s)
Obesidad , Sobrepeso , Adulto , Humanos , Estudios Transversales , Obesidad/epidemiología , Obesidad/prevención & control , Sobrepeso/epidemiología , Gobierno , Políticas , Impuestos
14.
Int J Obes (Lond) ; 48(1): 78-82, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37770575

RESUMEN

BACKGROUND: Education about the prevalent chronic disease of obesity is still minimal and variable in medical school curricula. In a student-led effort with faculty support, the authors designed and implemented an obesity medicine elective at Case Western Reserve University School of Medicine (CWRU). The 10-week elective, taught by seven physicians and one dietitian, was offered in January 2023 to medical students and included: weekly lectures, an interactive session with a patient, shadowing in obesity medicine practices, attendance at a distance-learning intensive behavioral lifestyle program, student presentations, and a final written reflection. The purpose of this study was to analyze the elective reflections and identify themes about the elective's value and areas to improve. METHODS: The authors analyzed reflections from the 20 medical students that completed the elective via qualitative thematic analysis. The analysis was performed using the Braun and Clarke six-phase framework: (1) become familiar with the data, (2) generate initial codes, (3) search for themes, (4) review themes, (5) define themes, and (6) write-up. RESULTS: The themes identified were improved: (1) understanding of obesity as a chronic disease, (2) knowledge about treatment options for obesity (3) confidence in compassionate obesity counseling skills, and (4) skills to confront weight bias. Theme (5) consisted of highlights (hearing from experts, practicing evidence-based medicine, and interacting with patients), and areas to improve (session length, presentation format, more peer-to-peer interaction, and more diverse patient interactions). CONCLUSIONS: Medical student assessments of a new obesity medicine elective described improved attitudes, knowledge, and skills to address obesity and obesity bias. Students were very satisfied and contributed ideas for improvements. This elective structure and evaluation method is a feasible model to provide medical students with meaningful experiences related to obesity.


Asunto(s)
Curriculum , Estudiantes de Medicina , Humanos , Retroalimentación , Obesidad/epidemiología , Obesidad/prevención & control , Enfermedad Crónica
15.
J Nutr ; 154(4): 1356-1367, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37984744

RESUMEN

BACKGROUND: Beginning in 1977, the U.S. Government began formally issuing dietary advice, a main objective of which was to reduce and prevent the prevalence of obesity in the American population. Concurrently, the Harvard School of Public Health began conducting dietary intake surveys and collecting body mass index (BMI) (kg/m2) data on female nurses in the Nurses' Health Study I (NHSI) and II (NHSII). OBJECTIVES: We aimed to assess whether compliance with the nutrition guidance from the U.S. Government to restrict dietary intake regarding total fat, saturated fat, and cholesterol was meaningfully associated with the prevalence of obesity. METHODS: We analyzed nutrition survey data from 1980 to 2011, grouping the sample into "compliers," those who complied with guidance on the intake of total fat, saturated fat, and cholesterol, and "noncompliers," those who did not. We then compared the means, medians, and distributions of BMI for compliers and noncompliers over the period for both the full survey population and an age-controlled sample. Finally, we plotted raw NHS data to examine respondents' Fat Proportion intake of energy and concurrent BMI. RESULTS: The mean and median BMI for both compliers and noncompliers increased throughout the sample period, and the BMI distributions shifted toward obese and severely obese overall and for an age-controlled subset compared with the 1980 NHSI and 1990 NHSII baselines. Compliers had slightly lower mean BMI increases than noncompliers but saw a relatively higher increase in the growth of the prevalence of those with BMI >30. We also found no linear relationship between Fat Proportion of energy intake and concurrent BMI. CONCLUSIONS: Guidance from the U.S. Government to limit fat, saturated fat, and cholesterol consumption was widely adopted by American female nurses during the study period. Our results show that compliance with this guidance had little if any effect in mitigating population-wide BMI increases during our study period.


Asunto(s)
Enfermeras y Enfermeros , Obesidad , Humanos , Femenino , Estados Unidos/epidemiología , Obesidad/epidemiología , Obesidad/prevención & control , Estado Nutricional , Índice de Masa Corporal , Ingestión de Energía , Encuestas Nutricionales , Colesterol , Ácidos Grasos , Grasas de la Dieta
16.
Milbank Q ; 102(2): 336-350, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38332667

RESUMEN

Policy Points Health policymakers have insufficiently addressed care for people with obesity (body mass index ≥ 30 kg/m2) in the United States. Current federal policies targeting obesity medications reflect this unfortunate reality. We argue for a novel policy framework to increase access to effective obesity therapeutics and care, recognizing that, though prevention is critical, the epidemic proportions of obesity in the United States warrant immediate interventions to augment care. Reducing barriers to and improving the quality of existing anti-obesity medications, intensive behavioral therapy, weight management nutrition and dietary counseling, and bariatric surgery are critical. Moreover, to ensure continuity of care and patient-clinician trust, combating physician and broader weight stigma must represent a central component of any viable obesity care agenda.


Asunto(s)
Política de Salud , Obesidad , Humanos , Estados Unidos , Obesidad/terapia , Obesidad/prevención & control , Cirugía Bariátrica , Accesibilidad a los Servicios de Salud , Fármacos Antiobesidad/uso terapéutico , Terapia Conductista
17.
Immunity ; 42(1): 133-44, 2015 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-25601202

RESUMEN

Long-term consumption of fatty foods is associated with obesity, macrophage activation and inflammation, metabolic imbalance, and a reduced lifespan. We took advantage of Drosophila genetics to investigate the role of macrophages and the pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich diet presented with increased fat storage, systemic activation of JAK-STAT signaling, reduced insulin sensitivity, hyperglycemia, and a shorter lifespan. Drosophila macrophages produced the JAK-STAT-activating cytokine upd3, in a scavenger-receptor (crq) and JNK-dependent manner. Genetic depletion of macrophages or macrophage-specific silencing of upd3 decreased JAK-STAT activation and rescued insulin sensitivity and the lifespan of Drosophila, but did not decrease fat storage. NF-κB signaling made no contribution to the phenotype observed. These results identify an evolutionarily conserved "scavenger receptor-JNK-type 1 cytokine" cassette in macrophages, which controls glucose metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via activation of the JAK-STAT pathway.


Asunto(s)
Envejecimiento Prematuro/inmunología , Proteínas de Drosophila/metabolismo , Drosophila/inmunología , Macrófagos/fisiología , Obesidad/prevención & control , Envejecimiento Prematuro/etiología , Envejecimiento Prematuro/genética , Animales , Células Cultivadas , Dieta Alta en Grasa/efectos adversos , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/inmunología , Humanos , Inflamación , Resistencia a la Insulina/genética , Quinasas Janus/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Activación de Macrófagos/genética , Obesidad/etiología , ARN Interferente Pequeño/genética , Receptores Depuradores/metabolismo , Factores de Transcripción STAT/metabolismo , Transducción de Señal
18.
EMBO Rep ; 23(7): e54132, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35652247

RESUMEN

Our knowledge of the coordination of intergenerational inheritance and offspring metabolic reprogramming by gastrointestinal endocrine factors is largely unknown. Here, we showed that secretin (SCT), a brain-gut peptide, is downregulated by overnutrition in pregnant mice and women. More importantly, genetic loss of SCT in the maternal gut results in undesirable phenotypes developed in offspring including enhanced high-fat diet (HFD)-induced obesity and attenuated browning of inguinal white adipose tissue (iWAT). Mechanistically, loss of maternal SCT represses iWAT browning in offspring by a global change in genome methylation pattern through upregulation of DNMT1. SCT functions to facilitate ubiquitination and degradation of DNMT1 by activating AMPKα, which contributes to the observed alteration of DNMT1 in progeny. Lastly, we showed that SCT treatment during pregnancy can reduce the development of obesity and improve glucose tolerance and insulin resistance in offspring of HFD-fed females, suggesting that SCT may serve as a novel biomarker or a strategy for preventing metabolic diseases.


Asunto(s)
Resistencia a la Insulina , Secretina , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Obesidad/genética , Obesidad/metabolismo , Obesidad/prevención & control , Embarazo , Secretina/metabolismo
19.
Int J Behav Nutr Phys Act ; 21(1): 15, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347579

RESUMEN

BACKGROUND: Improving physical activity and reducing sedentary behavior represent important areas for intervention in childhood in order to reduce the burden of chronic disease related to obesity and physical inactivity in later life. This paper aims to determine the cost-effectiveness of a multi-arm primary school-based intervention to increase physical activity and/or reduce sedentary time in 8-9 year old children (Transform-Us!). METHODS: Modelled cost-utility analysis, using costs and effects from a cluster randomized controlled trial of a 30-month intervention that used pedagogical and environmental strategies to reduce and break up sedentary behaviour (SB-I), promote physical activity (PA-I), or a combined approach (PA + SB-I), compared to current practice. A validated multiple-cohort lifetable model (ACE-Obesity Policy model) estimated the obesity and physical activity-related health outcomes (measured as change in body mass index and change in metabolic equivalent task minutes respectively) and healthcare cost-savings over the cohort's lifetime from the public-payer perspective, assuming the intervention was delivered to all 8-9 year old children attending Australian Government primary schools. Sensitivity analyses tested the impact on cost-effectiveness of varying key input parameters, including maintenance of intervention effect assumptions. RESULTS: Cost-effectiveness results demonstrated that, when compared to control schools, the PA-I and SB-I intervention arms were "dominant", meaning that they resulted in net health benefits and healthcare cost-savings if the intervention effects were maintained. When the costs and effects of these intervention arms were extrapolated to the Australian population, results suggested significant potential as obesity prevention measures (PA-I: 60,780 HALYs saved (95% UI 15,007-109,413), healthcare cost-savings AUD641M (95% UI AUD165M-$1.1B); SB-I: 61,126 HALYs saved (95% UI 11,770 - 111,249), healthcare cost-savings AUD654M (95% UI AUD126M-1.2B)). The PA-I and SB-I interventions remained cost-effective in sensitivity analysis, assuming the full decay of intervention effect after 10 years. CONCLUSIONS: The PA-I and SB-I Transform-Us! intervention arms represent good value for money and could lead to health benefits and healthcare cost-savings arising from the prevention of chronic disease in later life if intervention effects are sustained. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN83725066). Australia and New Zealand Clinical Trials Registry Number (ACTRN12609000715279).


Asunto(s)
Promoción de la Salud , Conducta Sedentaria , Niño , Humanos , Análisis Costo-Beneficio , Promoción de la Salud/métodos , Australia , Ejercicio Físico , Obesidad/prevención & control , Instituciones Académicas , Enfermedad Crónica
20.
Int J Behav Nutr Phys Act ; 21(1): 63, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867226

RESUMEN

BACKGROUND: Islamic leaders, staff, and Muslim parents in the UK are supportive of healthy lifestyle intervention delivery through Islamic Religious Settings. Such interventions are necessary given high obesity rates in British South Asian (40%) compared to White British (32%) children of equivalent age. Co-production can facilitate the development of culturally appropriate health interventions, however it can be theoretically and practically challenging, and evaluation of co-production within an Islamic Religious Setting context is lacking. The aim of this study was to examine the feasibility and acceptability of taking a co-production approach to develop an obesity-prevention toolkit for Islamic Religious Settings. METHODS: An obesity-prevention toolkit for use in Islamic Religious Settings, incorporating physical activity, healthy diet, and organisational change, has been co-produced to be evidence-informed and contextually relevant. A qualitative process evaluation was employed to examine experiences of co-production. Semi-structured interviews (n = 15) and a focus group (n = 5) were conducted with toolkit co-production stakeholders, e.g., subject experts, an Islamic scholar, and Islamic Religious Setting staff. Transcripts were analysed inductively using reflexive thematic analysis. RESULTS: The analysis revealed four major themes regarding stakeholders' experiences of co-producing a childhood obesity-prevention toolkit for Islamic Religious Settings. These themes are: (1) attitudes towards obesity-prevention through Islamic Religious Settings, (2) benefits of co-production including capacity building and ownership (3) negotiating involvement, power, and perspectives within the co-production process, and (4) the complexities of effective communication in co-production. CONCLUSION: This study adds to the evidence-base in support of delivering health promotion through faith settings. Taking a co-production approach to develop an obesity-prevention toolkit for Islamic Religious Settings provided benefit to the toolkit product and local stakeholders. The toolkit is currently being implemented across Bradford, UK and there is potential to adapt the toolkit to other geographical contexts, and for evaluating effectiveness for preventing obesity in British Muslim families.


Asunto(s)
Promoción de la Salud , Islamismo , Investigación Cualitativa , Humanos , Promoción de la Salud/métodos , Femenino , Masculino , Grupos Focales , Obesidad/prevención & control , Reino Unido , Ejercicio Físico , Obesidad Infantil/prevención & control , Adulto , Niño , Dieta Saludable/métodos
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