title: Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.
abstract: Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.forename: Hwi Jin
authors.initials: HJ
authors.lastname: Ko
authors.forename: Eben I
authors.initials: EI
authors.lastname: Lichtman
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lawton
authors.forename: Helena
authors.initials: H
authors.lastname: Ong
authors.forename: Kristine
authors.initials: K
authors.lastname: Yu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Azuma
authors.forename: Randall H
authors.initials: RH
authors.lastname: Friedline
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015153:Blotting, Western; D001823:Body Composition / Q000502:physiology; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology; D007249:Inflammation / Q000473:pathology*; D007333:Insulin Resistance / Q000502:physiology*; D007378:Interleukins / Q000097:blood; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000473:pathology*; D010805:Physical Conditioning, Animal / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015431:Weight Loss / Q000502:physiology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007378:Interleukins; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: exercise; inflammation; insulin resistance; obesity; weight loss