Porcine adiponectin receptor 1 transgene resists high-fat/sucrose diet-induced weight gain, hepatosteatosis and insulin resistance in mice
Journal
Experimental Animals
Journal Volume
62
Journal Issue
4
Pages
347-360
Date Issued
2013
Author(s)
Liu, B.-H.
Lin, Y.-Y.
Wang, Y.-C.
Huang, C.-W.
Chen, C.-C.
Wu, S.-C.
Mersmann, H.J.
Cheng, W.T.K.
Abstract
Adiponectin and its receptors have been demonstrated to play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with down-regulated adiponectin signaling. In this study, we generated mice overexpressing the porcine Adipor1 transgene (pAdipor1) to study its benefcial effects in metabolic syndromes as expressed in diet-induced obesity, hepatosteatosis and insulin resistance. Wild-type (WT) and pAdipor1 transgenic mice were fed ad libitum with a standard chow diet (Chow) or a high-fat/sucrose diet (HFSD) for 24 weeks, beginning at 6 to 7 weeks of age. There were 12 mice per genetic/diet/ sex group. When challenged with HFSD to induce obesity, the pAdipor1 transgenic mice resisted development of weight gain, hepatosteatosis and insulin resistance. These mice had lowered plasma adiponectin, triglyceride and glycerol concentrations compared to WT mice. Moreover, we found that (indicated by mRNA levels) fatty acid oxidation was enhanced in skeletal muscle and adipose tissue, and liver lipogenesis was inhibited. The pAdipor1 transgene also restored HFSD-reduced phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose transporter 4 mRNA in the adipose tissues, implying that the increased Pck1 may promote glyceroneogenesis to reduce glucose intolerance and thus activate the flux of glyceride-glycerol to resist diet-induced weight gain in the adipose tissues. Taken together, we demonstrated that pAdipor1 can prevent diet-induced weight gain and insulin resistance. Our findings may provide potential therapeutic strategies for treating metabolic syndromes and obesity, such as treatment with an ADIPOR1 agonist or activation of Adipor1 downstream targets. ? 2013 Japanese association for Laboratory animal Science.
SDGs
Other Subjects
adiponectin receptor 1; glucose transporter 4; glycerol; messenger RNA; phosphoenolpyruvate carboxykinase (GTP); triacylglycerol; ADIPOR1 gene; adipose tissue; animal experiment; animal model; animal tissue; article; controlled study; fatty acid oxidation; fatty liver; female; gene; glucose intolerance; glycerol blood level; insulin resistance; lipid diet; lipogenesis; male; metabolic syndrome X; mouse; nonhuman; nucleotide sequence; obesity; PCK1 gene; skeletal muscle; sugar intake; transgene; transgenic mouse; triacylglycerol blood level; weight gain; wild type; Adipose Tissue; Animals; Diet, High-Fat; Dietary Sucrose; Fatty Liver; Female; Gluconeogenesis; Glucose Transporter Type 4; Insulin Resistance; Intracellular Signaling Peptides and Proteins; Lipogenesis; Male; Metabolic Syndrome X; Mice; Mice, Transgenic; Molecular Targeted Therapy; Obesity; Phosphoenolpyruvate Carboxykinase (GTP); Receptors, Adiponectin; Swine; Transgenes; Up-Regulation; Weight Gain
Type
journal article