Loss of resistin improves glucose homeostasis in leptin deficiency.
Resistin levels are increased in obesity, and hyperresistinemia impairs glucose homeostasis in rodents. Here, we have determined the role of resistin in ob/ob mice that are obese and insulin resistant because of genetic deficiency of leptin. Loss of resistin increased obesity in ob/ob mice by further lowering the metabolic rate without affecting food intake. Nevertheless, resistin deficiency improved glucose tolerance and insulin sensitivity in these severely obese mice, largely by enhancing insulin-mediated glucose disposal in muscle and adipose tissue. In contrast, in C57BL/6J mice with diet-induced obesity but wild-type leptin alleles, resistin deficiency reduced hepatic glucose production and increased peripheral glucose uptake. Resistin deficiency enhanced Akt phosphorylation in muscle and liver and decreased suppressor of cytokine signaling-3 level in muscle, and these changes were reversed by resistin replacement. Together, these results provide strong support for an important role of resistin in insulin resistance and diabetes associated with genetic or diet-induced obesity.
Qi
Yong
Y
University of Pennsylvania School of Medicine, Division of Endocrinology, DiabetesMetabolism, 764 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104, USA.
Nie
Zhenying
Z
Lee
Yun-Sik
YS
Singhal
Neel S
NS
Scherer
Philipp E
PE
Lazar
Mitchell A
MA
Ahima
Rexford S
RS
D000375:Aging; D000818:Animals; D004435:Eating; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D020738:Leptin / Q000172:deficiency* / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010101:Oxygen Consumption; D052243:Resistin / Q000172:deficiency* / Q000235:genetics
D020738:Leptin; D052243:Resistin; D005947:Glucose