title: Porcine adiponectin receptor 1 transgene resists high-fat/sucrose diet-induced weight gain, hepatosteatosis and insulin resistance in mice.
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 beneficial 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.
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Da'an Dist., Taipei City 106, Taiwan.
authors.forename: Bing-Hsien
authors.initials: BH
authors.lastname: Liu
authors.forename: Yuan-Yu
authors.initials: YY
authors.lastname: Lin
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Wang
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Huang
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Chen
authors.forename: Shinn-Chih
authors.initials: SC
authors.lastname: Wu
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Mersmann
authors.forename: Winston T K
authors.initials: WT
authors.lastname: Cheng
authors.forename: Shih-Torng
authors.initials: ST
authors.lastname: Ding
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics*; D005260:Female; D005943:Gluconeogenesis / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050155:Lipogenesis / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control / Q000628:therapy; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000502:physiology*; D013552:Swine; D019076:Transgenes / Q000235:genetics* / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics; D015430:Weight Gain / Q000235:genetics*
chemical_list: D019422:Dietary Sucrose; D051275:Glucose Transporter Type 4; D047908:Intracellular Signaling Peptides and Proteins; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)