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Am J Physiol Endocrinol Metab. 2019 Aug 13. doi: 10.1152/ajpendo.00102.2019. [Epub ahead of print]

The TRPV1 channel regulates glucose metabolism.

Author information

1
Adelaide Medical School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia. South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia. Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia.
2
Adelaide Medical School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia. South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia.
3
Adelaide Medical School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia. South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia. Freemasons Foundation Centre for Men's Health, The University of Adelaide, Adelaide, SA, 5005, Australia.
4
Adelaide Medical School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia.

Abstract

Endocannabinoids (ECs) mediate effects via cannabinoid receptors type1&2 (CB1&2) and TRPV1 channels. In high fat diet (HFD)-induced obese mice overactivity of the EC system and inhibition of CB1 increases skeletal muscle glucose uptake. We explored the role of TRPV1. Male TRPV1+/+(WT) and TRPV1-/-(KO)-mice were fed (20wks) standard (SLD) or HFD. Intraperitoneal glucose tolerance test was performed. RT-PCR was performed to measure mRNA of genes involved in glucose/lipid metabolism and the EC system in soleus (SOL) and extensor digitorum longus (EDL) muscles. Cultured L6-cells were used to measure glucose uptake in skeletal muscle. HFD-mice weighed more and had higher insulin levels than SLD-mice with no genotype differences. Basal and peak glucose was higher in HFD-mice irrespective of genotype but glucose cleared faster in HFD/WT vs HFD/KO-mice. 2-arachidonoylglycerol augmented insulin induced glucose uptake in skeletal L6-cells, an effect blocked by the TRPV1 antagonist SB366791. In EDL, fatty acid amide hydrolase (FAAH) mRNA was increased in KO vs WT-mice, irrespective of diet. Pyruvate dehydrogenase kinase isozyme4 (PDK4) and mitochondrial uncoupling protein3 (UCP3) were elevated and FA desaturase2 (FADS2) mRNA lower in HFD-mice, irrespective of genotype. CB1 and stearoyl-CoA desaturase (SCD1) were lower in HFD/WT-mice only. In SOL, PDK4, UCP3, hormone-sensitive lipase (LIPE), fatty acid translocase (CD36) and Carnitine Palmitoyl Transferase2 (CPT2) were elevated and, SCD1, FAAH, FADS2 and Troponin1 (TNNC1) mRNA lower in HFD-mice, irrespective of genotype. In conclusion, TRPV1 regulates glucose disposal in HFD-mice. We propose TRPV1 plays a role coordinating glucose metabolism in EDL under conditions of metabolic stress.

KEYWORDS:

Extensor digitorum longus; High fat diet; Metabolism; Soleus; TRPV1

PMID:
31408376
DOI:
10.1152/ajpendo.00102.2019

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