Porcine Adiponectin Receptor 1 Transgene Resists High-fat/Sucrose
Diet-Induced Weight Gain,Hepatosteatosis and Insulin Resistance in Mice |
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Authors: | Bing-Hsien Liu Yuan-Yu Lin Ya-Chin Wang Chao-Wei Huang Chih-Chien Chen Shinn-Chih Wu Harry J Mersmann Winston TK Cheng Shih-Torng Ding |
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Institution: | 1)Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Da’an Dist., Taipei City 106, Taiwan;2)Institute of Biotechnology, National Taiwan University, No.81, Changxing St., Da’an Dist., Taipei City 106, Taiwan;3)Department of Animal Science and Biotechnology, Tunghai University, No.1727, Sec. 4, Taiwan Blvd., Xitum Dist., Taichung City 407, Taiwan |
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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. |
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Keywords: | adiponectin receptor 1 diet-induced obesity insulin resistance pig |
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