| You deserve what you eat: lessons learned from the study of the melanin-concentrating hormone (MCH)-deficient mice. | |
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MedLine Citation:
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PMID: 20966023 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Diet plays a crucial role in the development of obesity and insulin resistance via multiple mechanisms. Saturated fatty acids can directly trigger tissue specific proinflammatory pathways via Toll-like receptor-4 (TLR4)-dependent mechanisms. Moreover, diet can change the gut microbiome and increase gut permeability. However, very few studies have addressed the obesity-independent role of diet. Dissecting the effects of diet from those of obesity per se will enhance our understanding of the underlying pathogenesis, and, at the translational level, advance our treatment approaches for obesity and its co-morbidities. METHODS: Melanin-concentrating hormone (MCH) is an important regulator of appetite and energy balance. MCH-deficient mice are resistant to diet-induced obesity, primarily due to increased locomotor activity. We took advantage of the unique phenotype of these mice to examine the metabolic and inflammatory consequences of a 15-week consumption of a diet high in saturated fat. RESULTS: MCH-deficient mice chronically exposed to a high-fat diet gain less weight compared to their wild-type littermates, despite similar food intake, and are protected from hepatosteatosis. They also lack obesity-associated upregulation of serum leptin and insulin levels and have improved total body insulin sensitivity. Nevertheless, we found indistinguishable liver-specific innate immune responses in both genotypes associated with high-fat feeding, which involved activation of TLR4 and its downstream effectors, MyD88, p38 MAP kinase and STAT-3. CONCLUSIONS: Our findings indicate that high-fat feeding is deleterious to the liver, independently of the obesity status. They also suggest that MCH is not necessary for the TLR4-dependent immune response triggered by the high-fat diet. |
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Authors:
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Yan Wang; Dimitrios C Ziogas; Sudha Biddinger; Efi Kokkotou |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-21 |
Journal Detail:
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Title: Gut Volume: 59 ISSN: 1468-3288 ISO Abbreviation: Gut Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-12 Completed Date: 2010-12-10 Revised Date: 2011-07-26 |
Medline Journal Info:
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Nlm Unique ID: 2985108R Medline TA: Gut Country: England |
Other Details:
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Languages: eng Pagination: 1625-34 Citation Subset: AIM; IM |
Affiliation:
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Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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metabolism Adiposity / physiology Animals Blood Glucose / metabolism Body Weight / physiology Dietary Fats / administration & dosage*, pharmacology Eating / physiology Gene Expression Regulation / drug effects Gluconeogenesis / drug effects, physiology Glucose Tolerance Test Hypothalamic Hormones / deficiency*, physiology Immunity, Innate Insulin / blood Leptin / blood Lipid Metabolism / drug effects, physiology Lipogenesis / drug effects, physiology Liver / immunology, metabolism Male Melanins / deficiency*, physiology Mice Mice, Knockout Pituitary Hormones / deficiency*, physiology Signal Transduction / physiology Thinness / metabolism, physiopathology Toll-Like Receptor 4 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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5 P30 CA06516/CA/NCI NIH HHS; R01 DK080058-03/DK/NIDDK NIH HHS; R01DK080058/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Dietary Fats; 0/Hypothalamic Hormones; 0/Leptin; 0/Melanins; 0/Pituitary Hormones; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 11061-68-0/Insulin; 67382-96-1/melanin-concentrating hormone |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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