Dataset Information

Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake.

ABSTRACT: Recent data have demonstrated that the hypothalamic GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates brown adipose tissue (BAT) thermogenesis by acting downstream on AMP-activated protein kinase (AMPK). Herein, we aimed to investigate whether genetic over-expression of GRP78 in the ventromedial nucleus of the hypothalamus (VMH: a key site regulating thermogenesis) could ameliorate very high fat diet (vHFD)-induced obesity. Our data showed that stereotaxic treatment with adenoviruses harboring GRP78 in the VMH reduced hypothalamic endoplasmic reticulum ER stress and reversed vHFD-induced obesity. Herein, we also demonstrated that this body weight decrease was more likely associated with an increased BAT thermogenesis and browning of white adipose tissue (WAT) than to anorexia. Overall, these results indicate that the modulation of GRP78 in the VMH may be a target against obesity.

SUBMITTER: Linares-Pose L

PROVIDER: S-EPMC6070933 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake.

Liñares-Pose Laura L Rial-Pensado Eva E Estévez-Salguero Ánxela Á Milbank Edward E González-García Ismael I Rodríguez Claudia C Seoane-Collazo Patricia P Martinez-Sánchez Noelia N Nogueiras Rubén R Prieto Dolores D Diéguez Carlos C Contreras Cristina C López Miguel M

Genes 20180717 7

Recent data have demonstrated that the hypothalamic GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates brown adipose tissue (BAT) thermogenesis by acting downstream on AMP-activated protein kinase (AMPK). Herein, we aimed to investigate whether genetic over-expression of GRP78 in the ventromedial nucleus of the hypothalamus (VMH: a key site regulating thermogenesis) could ameliorate very high fat diet (vHFD)-induced obesity. Our data showed that stereotaxic tre ...[more]

PMID: 30018241

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Project description:Background and aimsHunger, satiation, postprandial satiety, and hedonic eating constitute key food intake parameters. We aim to study whether these symptoms are associated with gastrointestinal symptoms (GIS) in patients with obesity.MethodsThis is a cross-sectional study of patients with obesity. Patients completed the following validated biomarkers and questionnaires: hunger was measured via visual analog scale (100 mm) following a standard meal, satiation was measured via ad libitum meal (calories to fullness; kcal), postprandial satiety was measured via gastric emptying scintigraphy (T1/2; mins), and hedonic eating was measured via the Hospital Anxiety and Depression Scale questionnaire. Participants completed the abridged Bowel Disease Questionnaire to evaluate their GIS. We calculated the odds ratios (ORs) adjusted for sex, weight, and age between food intake parameters <25th or >75th percentile observed in a prior cohort of 450 participants with obesity and GIS.ResultsA total of 274 participants (41 ± 10 [SD] years, 75% females, body mass index 39 ± 8 kg/m2) were included in the analysis. Increased hunger was associated with a lower prevalence of lumpy stools (OR = 0.18, P = .02). Satiation was associated with abdominal pain/discomfort (relieved by defecation [OR = 2.4, P = .02] or associated with change in stool consistency [OR = 2.92, P < .01]), loose/watery stools (OR = 2.09, P = .02), and bloating (OR = 2.49, P < .01). Abnormal postprandial satiety was associated with bloating (OR = 2.26, P < .01) and loose/watery stools (OR = 1.84, P = .04). Hedonic eating was associated with abdominal pain/discomfort with stool frequency change (OR = 2.4, P = .02), >3 bowel movements per day (OR = 1.93, P = .048), bloating (OR = 2.49, P = .01), abdominal pain after meals >1 per month (OR = 4.24, P < .01), and nausea >1 per week (OR = 4.51, P < .01).ConclusionAlterations in hunger, satiation, postprandial satiety, and hedonic eating are associated with GIS in patients with obesity.

Dataset Information

Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake.

Publications

Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake.

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