Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl–CoA carboxylase inhibition and AMP-activated protein kinase activation

By E. Tomás, T. Tsao, A. Saha, H. Murrey, C. Zhang, Samar I. Itani, H. Lodish, N. Ruderman. Proceedings of the National Academy of Sciences of the United States of America, 2002

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gACRP30, the globular subunit of adipocyte complement-related protein of 30 kDa (ACRP30), improves insulin sensitivity and increases fatty acid oxidation. The mechanism by which gACRP30 exerts these effects is unknown. Here, we examined if gACRP30 activates AMP-activated protein kinase (AMPK), an enzyme that has been shown to increase muscle fatty acid oxidation and insulin sensitivity. Incubation of rat extensor digitorum longus (EDL), a predominantly fast twitch muscle, with gACRP30 (2.5 μg/ml) for 30 min led to 2-fold increases in AMPK activity and phosphorylation of both AMPK on Thr-172 and acetyl CoA carboxylase (ACC) on Ser-79. Accordingly, concentration of malonyl CoA was diminished by 30%. In addition, gACRP30 caused a 1.5-fold increase in 2-deoxyglucose uptake. Similar changes in malonyl CoA and ACC were observed in soleus muscle incubated with gACRP30 (2.5 μg/ml), although no significant changes in AMPK activity or 2-deoxyglucose uptake were detected. When EDL was incubated with full-length hexameric ACRP30 (10 μg/ml), AMPK activity and ACC phosphorylation were not altered. Administration of gACRP30 (75 μg) to C57 BL/6J mice in vivo led to increased AMPK activity and ACC phosphorylation and decreased malonyl CoA concentration in gastrocnemius muscle within 15–30 min. Both in vivo and in vitro, activation of AMPK was the first effect of gACRP30 and was transient, whereas alterations in malonyl CoA and ACC occurred later and were more sustained. Thus, gACRP30 most likely exerts its actions on muscle fatty acid oxidation by inactivating ACC via activation of AMPK and perhaps other signal transduction proteins.

Subfields: Geriatrics and Gerontology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/67c84c3ce656624642b781cda210adababe45972

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Citations in the corpus

APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function (2006, background): “AMPK has an important function in adiponectin-stimulated fatty-acid oxidation in muscle as it mediates the phosphorylation and inhibition of acetyl-CoA carboxylase ( ACC”
Adiponectin Regulation and Function (2018, positive): “Globular and full-length adiponectin phosphorylate and activate AMPK in skeletal muscle, resulting in increased phosphorylation of ACC, fatty acid oxidation and glucose uptake (330, 382).”
Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis in Diabetic LDL Receptor–Deficient Mice (2006, methodology): “AMPK activity in 1 or 2 immunocomplexes was measured using the SAMS peptide phosphorylation assay as described previously (19).”
Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. (2003, background): “[102] Tomas E, Tsao TS, Saha AK, Murrey HE, Zhang CcC, Itani SI,”
The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. (2004, background): “Two reports have recently demonstrated that adiponectin activates a specific kinase called AMP-activated protein kinase (AMPK), which has important metabolic consequences because it activates glucose transport in muscles by a mechanism that is not entirely understood (49,50).”
Mechanisms of obesity-associated insulin resistance: many choices on the menu. (2007, background): “In muscle, adiponectin stimulates glucose use and FA oxidation probably via activation of the cellular fuel sensor, AMP-activated protein kinase (AMPK) (Fruebis et al. 2001; Tomas et al. 2002; Yamauchi et al. 2002).”