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.

Adiponectin and adiponectin receptor 1 overexpression enhance inflammatory bowel disease

“…It suggests that mouse ADN binds to porcine AdipoR1 in pAdipoR1 mice. Moreover, we reported that the overexpression of pAdipoR1 resists the weight gain, hepatosteatosis, insulin resistance and heart hypertrophy in mice fed a high-fat/sucrose diet [ 33 , 46 , 47 ]. These results suggest that up-regulation of AdipoR1 might be a potential strategy for therapy of metabolism-related diseases.…”

“…pAdipoR1 mice were generated as previously reported [ 33 ]. Both wild type (WT) and transgenic mice were maintained under the same breeding conditions, and with the same diet fed ad libitum to ensure similar intestinal microflora.…”

A Newly Designed EGFP-2A Peptide Monocistronic Baculoviral Vector for Concatenating the Expression of Recombinant Proteins in Insect Cells

“…Interestingly, different ADN multimers activate different signal transduction pathways, while the ADN multimer species can be changed by the protein synthesis process of different eukaryotic donor cells because of the difference of the posttranslational modification system and variation of amino acids sequences within a eukaryote or even among animal species [21,28]. Mice expressing porcine ADN receptors are resistant to the development of weight gain, hepatosteatosis, and insulin resistance [36]. To address the mechanism of these porcine receptors in adipose tissue, our recombinant porcine ADN will be a valuable tool.…”

Adiponectin receptor 1 resists the decline of serum osteocalcin and GPRC6A expression in ovariectomized mice

“…In this study, in ovariectomized mice, we demonstrated that ApN signaling may mediate the function of Ocn in glucose homeostasis by interacting with GPRC6A, the putative receptor of Ocn. Our previous study showed that overexpression of AdipoR1 causes resistance to high fat / high sucrose diet induced-weight gain and glucose intolerance in mice [ 18 ]. Furthermore, AdipoR1 transgenic mice have higher serum Ocn than wild-type mice suggesting that Ocn may modulate glucose homeostasis via ApN signaling [ 9 ].…”

“…Generation and breeding strategies for AdipoR1 transgenic mice are described in a previous report [ 18 ]. The founder mice were crossed with wild-type (WT) mice to generate the F1 heterozygous (AdipoR1 +/− ) offspring and then backcrossed to the WT to generate the F2.…”