Estradiol overcomes adiponectin-resistance in diabetic mice by regulating skeletal muscle adiponectin receptor 1 expression

Objective: It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and/or oxidation in muscle. We aimed to determine changes in plasma adiponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial; HFA) and following pharmacological inhibition of adipose tissue lipolysis (low FFA trial; LFA). Furthermore, we aimed to detect and locate adiponectin in skeletal muscle tissue. Methods: Ten subjects performed two exercise trials (120 min at 50% VO2max). Indirect calorimetry was used to determine total fat oxidation rate. Plasma samples were collected at rest, during exercise and during post-exercise recovery to determine adiponectin, FFA and glycerol concentrations. Muscle biopsies were taken to determine adiponectin protein and adiponectin receptor 1 and 2 mRNA expression and to localise intramyocellular adiponectin. Results: Basal plasma adiponectin concentrations averaged 6.57±0.7 and 6.63±0.8 mg/l in the HFA and LFA trials respectively, and did not change significantly during or after exercise. In the LFA trial, plasma FFA concentrations and total fat oxidation rates were substantially reduced. However, plasma adiponectin and muscle adiponectin receptor 1 and 2 mRNA expression did not differ between trials. Immunohistochemical staining of muscle cross-sections showed the presence of adiponectin in the sarcolemma of individual muscle fibres and within the interfibrillar arterioles. Conclusion: Plasma adiponectin concentrations and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by changes in adipose tissue lipolysis and/or plasma FFA concentrations. Adiponectin is abundantly expressed in muscle, and, for the first time, it has been shown to be present in/on the sarcolemma of individual muscle fibres.

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Exercise Training Improves Whole Body Insulin Resistance via Adiponectin Receptor 1

International Journal of Sports Medicine ◽

10.1055/s-0035-1559715 ◽

2015 ◽

Vol 36 (13) ◽

pp. e24-e30 ◽

Cited By ~ 4

Author(s):

J.-K. Cho ◽

S.-U. Kim ◽

H.-R. Hong ◽

J.-H. Yoon ◽

H.-S. Kang

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Dietary Treatment ◽

Sirtuin 1 ◽

Adiponectin Receptor ◽

Whole Body ◽

Peroxisome Proliferator ◽

Down Regulation ◽

Peroxisome Proliferator Activated Receptor ◽

Adiponectin Receptor 1

AbstractLittle is known regarding whether adiponectin receptors mediate high-intensity interval training (HIT)-induced improvement of insulin resistance associated with obesity. This study investigated the effect of HIT on whole body insulin resistance in high-fat diet-induced obese mice. 5-week-old male mice (N=30) were randomly assigned to standard chow (SC) (n=10) or HFD (n=20) for 23 weeks. After 15 weeks of dietary treatment, the HFD mice were further assigned to HFD (n=10) or HFD plus HIT (HFD+HIT, n=10). The HFD+HIT mice were subjected to HIT during the last 8 weeks of the 23-week HFD course. HFD resulted in whole body insulin resistance, hypoadiponectinemia, suppressed expression of adiponectin receptor 1(AdipoR1) and 2 (AdipoR2), suppressed expression of phosphorylated AMP-activated protein kinase (p-AMPK) and NAD-dependent deacetylase sirtuin-1 (SIRT1), and decreased mRNAs of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferase I (CPT1), and acyl CoA oxidase (ACO) in skeletal muscle. In contrast, HIT alleviated whole body insulin resistance and prevented decreased levels of total adiponectin in both serum and adipose tissue. HIT also prevented the down-regulation of AdipoR1 and AMPK/SIRT1 proteins and the down-regulation of PPARα, CPT1, and ACO mRNAs. The current findings show that HIT alleviates whole body insulin resistance due to HFD-induced obesity via the AdipoR1 and AMPK/SIRT1 mediated-signaling pathway in skeletal muscle, implying the potential role of HIT to combat this metabolic condition.

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Elevation of circulating free fatty acids abolishes down-regulation of skeletal muscle adiponectin receptor 1 (AdipoR1) expression caused by insulin infusion

Endocrine Abstracts ◽

10.1530/endoabs.32.p346 ◽

2013 ◽

Author(s):

Marek Straczkowski ◽

Monika Karczewska-Kupczewska ◽

Agnieszka Adamska ◽

Magdalena Stefanowicz ◽

Natalia Matulewicz ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Free Fatty Acids ◽

Insulin Infusion ◽

Adiponectin Receptor ◽

Down Regulation ◽

Adiponectin Receptor 1

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PS 13-12 EXPRESSION OF ADIPONECTIN RECEPTOR 1 IN SKELETAL MUSCLE OF PEOPLE WITH HYPERTENSION IN THEIR YOUNG AND MIDDLE AGE

Journal of Hypertension ◽

10.1097/01.hjh.0000501106.02621.67 ◽

2016 ◽

Vol 34 (Supplement 1) ◽

pp. e428

Author(s):

Anastasia Sakovskaia ◽

Vera Nevzorova

Keyword(s):

Skeletal Muscle ◽

Middle Age ◽

Adiponectin Receptor ◽

Adiponectin Receptor 1

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Combination of Canagliflozin and Exercise Training Leads to Lipid-Dependent Energy Expenditure in Skeletal Muscle in Obese Diabetic Mice

Diabetes ◽

10.2337/db18-742-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 742-P

Author(s):

KENICHI TANAKA ◽

HIROKAZU TAKAHASHI ◽

KAZUYO SASAKI ◽

KANAKO INOUE ◽

YAYOI MATSUDA ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Expenditure ◽

Exercise Training ◽

Diabetic Mice

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Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival

Nature Communications ◽

10.1038/ncomms7228 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 42

Author(s):

Dennis S. Rice ◽

Jorgelina M. Calandria ◽

William C. Gordon ◽

Bokkyoo Jun ◽

Yongdong Zhou ◽

...

Keyword(s):

Docosahexaenoic Acid ◽

Opposite Effect ◽

Photoreceptor Cell ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Adiponectin Receptor ◽

Cell Integrity ◽

Photoreceptor Degeneration ◽

Adiponectin Receptor 1

Abstract The identification of pathways necessary for photoreceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of adiponectin receptor 1 (AdipoR1) as a regulator of these cells’ functions. Docosahexaenoic acid (DHA) is avidly retained in photoreceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoreceptor and RPE cell AdipoR1 expression, blunted in AdipoR1−/− mice. We also find decreased photoreceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoreceptor degeneration in AdipoR1−/− mice. RPE-rich eyecup cultures from AdipoR1−/− reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoreceptors and RPE, thus preserving photoreceptor cell integrity.

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