Poster Presentation Australian & New Zealand Obesity Society 2015 Annual Scientific Meeting

TRPV1 Channels: fibre type and diet specific integration of glucose and lipid metabolism in skeletal muscle. (#239)

George Hatzinikolas 1 2 , Amanda J Page 1 2 3 , Stephen J Kentish 1 2 , Paul Cavuoto 1 , Gary A Wittert 1 2 3
  1. Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide, Adelaide, SA, Australia
  2. South Australian Health and Medical Research Institute,, Adelaide, SA, Australia
  3. Royal Adelaide Hospital, Adelaide, SA, Australia

Aims: Endocannabinoids mediate action via cannabinoid receptors type 1&2 (CNR1&2) and TRPV1 channels. In obese mice, inhibition of CNR1 increases skeletal muscle glucose uptake (1). We explored the role of TRPV1 in vitro and in-vivo.

Methods: 8wk old male TRPV1+/+ (WT) and -/- (KO) mice were fed standard (SLD; 12% energy from fat) or high fat diet (HFD; 60% energy from fat) for 20wks. An intraperitoneal glucose tolerance test (IPGTT) was performed at 0 and 19wks. After 20wks, blood, soleus (SOL) and extensor digitorum longus (EDL) muscles were collected and mRNA of genes involved in glucose and lipid metabolism and the endocannabinoid system were measured by qPCR.

Results: Baseline weight was similar in WT and KO mice. At week 19, HFD mice weighed more and had higher insulin levels than SLD mice with no genotype differences. Blood glucose response to IPGTT was similar in WT and KO mice at baseline. At 19wks, basal and peak glucose was higher in HFD mice irrespective of genotype but glucose cleared faster in HFD/WT compared to HFD/KO mice.

Fatty acid amide hydrolase (FAAH) mRNA was increased in EDL of SLD/KO and HFD/KO mice. In EDL, pyruvare dehydrogenase kinase isozyme4 (PDK4) and mitochondrial uncoupling protein3 (UCP3) mRNA were elevated whereas FA desaturase2 (FADS2) mRNA was lower in HFD/WT and HFD/KO mice compared to SLD mice. CNR1 and stearoyl-CoA desaturase (SCD1) were lower in HFD/WT only. In SOL, PDK4, UCP3, hormone-sensitive lipase (LIPE), fatty acid translocase (CD36) and Carnitine Palmitoyl Transferase2 (CPT2) mRNA were elevated whereas SCD1, FAAH, FADS2 and Troponin1 (TNNC1) mRNA were reduced in HFD/WT and HFD/KO mice.

Conclusion: TRPV1 may regulate glucose disposal in HFD-induced obesity. We propose TRPV1 plays a role in coordinating lipid and glucose metabolism in EDL muscle under conditions of metabolic stress.

Funding: Gum Bequest, Royal Adelaide Hospital

  1. Best Pract Res Clin Endocrinol Metab. 2009 23(1): 79-86