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      Adiponectin regulates the circadian rhythm of glucose and lipid metabolism

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          Abstract

          Adiponectin is a cytokine secreted from adipocytes and regulates metabolism. Although serum adiponectin levels show diurnal variations, it is not clear if the effects of adiponectin are time-dependent. Therefore, this study conducted locomotor activity analyses and various metabolic studies using the adiponectin knockout (APN (−/−)) and the APN (+/+) mice to understand whether adiponectin regulates the circadian rhythm of glucose and lipid metabolism. We observed that the adiponectin gene deficiency does not affect the rhythmicity of core circadian clock genes expression in several peripheral tissues. In contrast, the adiponectin gene deficiency alters the circadian rhythms of liver and serum lipid levels and results in the loss of the time dependency of very-low-density lipoprotein-triglyceride secretion from the liver. In addition, the whole-body glucose tolerance of the APN (−/−) mice was normal at CT10 but reduced at CT22, compared to the APN (+/+) mice. The decreased glucose tolerance at CT22 was associated with insulin hyposecretion in vivo. In contrast, the gluconeogenesis activity was higher in the APN (−/−) mice than in the APN (+/+) mice throughout the day. These results indicate that adiponectin regulates part of the circadian rhythm of metabolism in the liver.

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          A simple method for the isolation and purification of total lipides from animal tissues.

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            Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.

            Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.
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              Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.

              Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6+/-0.4 versus 7.9+/-0.5 microg/mL in men, 7.6+/-0.7 versus 11.7+/-1.0 microg/mL in women; P<0.001). The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD (4.0+/-0.4 versus 6.6+/-0.4 microg/mL, P<0.001 in men; 6.3+/-0.8 versus 7.6+/-0. 7 microg/mL in women). In contrast, plasma levels of leptin did not differ between diabetic patients with and without CAD. The presence of microangiopathy did not affect the plasma adiponectin levels in diabetic patients. Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels. In multivariate analysis, plasma insulin did not independently affect the plasma adiponectin levels. BMI, serum triglyceride concentration, and the presence of diabetes or CAD remained significantly related to plasma adiponectin concentrations. Weight reduction significantly elevated plasma adiponectin levels in the diabetic subjects as well as the nondiabetic subjects. These results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy.

                Author and article information

                Journal
                J Endocrinol
                J Endocrinol
                JOE
                The Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0022-0795
                1479-6805
                06 June 2022
                01 August 2022
                : 254
                : 2
                : 121-133
                Affiliations
                [1 ]Laboratory of Health Science , School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
                [2 ]Laboratory of Organic Chemistry , School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
                [3 ]Department of Psychiatry , Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
                [4 ]Tokyo Adachi Hospital , Adachi, Tokyo, Japan
                [5 ]Department of Biological Sciences , School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
                Author notes
                Correspondence should be addressed to S Shimba: shimba.shigeki@ 123456nihon-u.ac.jp
                Author information
                http://orcid.org/0000-0002-5302-8387
                Article
                JOE-22-0006
                10.1530/JOE-22-0006
                9354065
                35662074
                aa3217fc-d31b-4ceb-8e3b-027b52ba3c3f
                © The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 05 May 2022
                : 03 June 2022
                Categories
                Research

                Endocrinology & Diabetes
                adiponectin,circadian rhythm,liver,metabolism,vldl,insulin
                Endocrinology & Diabetes
                adiponectin, circadian rhythm, liver, metabolism, vldl, insulin

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