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- Title
Deletion of Apolipoprotein D Prevents Diet-Induced Obesity and Insulin Resistance.
- Authors
Jung, Dae Young; Zhang, Zhiyou; Kim, Jae Hyeong; Park, Soyoung; Cho, You-Ree; Pentchev, Peter G.; Buhman, Kimberly; Ghoshal, Saheli; Patel, Shutish; Kim, Jason K.
- Abstract
Apolipoprotein D (apoD) is a member of the lipocalin superfamily of transporters that is expressed in neural and peripheral tissues and shown to interact with LXR/RXR heterodimers in adipocytes. The metabolic role of apoD was examined using a hyperinsulinemic (2.5 mU/kg/min)-euglycemic clamp in awake apoD KO and wild-type (WT) mice fed standard chow or high-fat diet (HFD) for 3 weeks (n=8∼11). [3-[sup 3]H]glucose and [l-[sup 14]C]2-deoxyglucose were administered during clamps to measure glucose metabolism in vivo. ApoD KO mice were resistant to diet-induced obesity with markedly reduced whole body fat mass (measured using [sup 1]H-MRS) compared to WT mice (Fig 1), and this was associated with significant increases in whole body energy expenditure (Fig 2), VO[sub 2] consumption and VCO[sub 2] production (measured using metabolic cages). ApoD deletion did not affect food intake (Fig 2), physical activity and intestinal fat absorption. HFD caused insulin resistance in WT mice, but apoD KO mice maintained normal insulin-stimulated whole body glucose turnover and skeletal muscle glucose uptake following HFD (Fig 3). The protective effects of apoD deletion on diet-induced insulin resistance was partly due to ∼50% increases in total IRS-1 expression and tyrosine phorphorylation of IRSI that were associated with reduced triglyceride level in skeletal muscle of HFD-fed apoD KO mice (Fig 4). ApoD KO mice were also protected from diet-induced insulin resistance in heart and adipose tissue. In contrast, apoD deletion did not affect basal hepatic glucose production and diet-induced changes in hepatic insulin action. Thus, these results indicate that apoD deletion prevents diet-induced obesity by increasing energy expenditure and insulin resistance by reducing intramuscular lipid and increasing IRS-associated insulin signaling in skeletal muscle. Our findings suggest that apoD plays an important role in energy balance and in the pathogenesis of obesity-associated type 2 diabetes.
- Subjects
APOLIPOPROTEINS; INSULIN resistance; INSULIN; OBESITY; TYPE 2 diabetes; LABORATORY mice
- Publication
Diabetes, 2007, Vol 56, pA454
- ISSN
0012-1797
- Publication type
Article