School of Pharmacy, University of Wyoming,
Department of Health and Exercise Science,
Colorado State University,
Department of Anesthesiology Clinical Research & Development, University of Colorado Denver.
Diet-induced obesity results from an imbalance between calorie intake and energy expenditure. This leads to several metabolic complications leading to type 2 diabetes, hypertension, and hyperlipidemia, all of which leading to cardiac dysfunction. The growing rate of adult and childhood obesity in US produces a severe burden on our health care system. Therefore, it is important to explore novel strategies to combat obesity and its comorbidities. Previous research suggests that targeting transient receptor potential vanilloid 1 (TRPV1) is a compelling target to abate diet-induced obesity. However, the mechanism by which TRPV1 activation prevents obesity still remains elusive. This research anchors on our hypothesis that TRPV1 expression and activation is important for preventing diet-induced obesity.
In order to understand the role of TRPV1 in obesity and metabolic syndrome, we evaluated whether genetic deletion of TRPV1 affects metabolism and thermogenesis. We determined the expression of adipogenic and thermogenic genes in normal chow diet (NCD) or high fat diet (60% calories from fat)-fed wild type and TRPV1-/- mice to understand the regulation of these gene expressions by endogenous TRPV1.
Mice were fed NCD or HFD for 32 weeks. We measured the respiratory quotient and heat out put in these mice. Also, we isolated epididymal, subcutaneous (inguinal) and brown fat pads (EF, SCF and BF, respectively) from these mice and analyzed the expression of adipogenic and thermogenic genes. We also determined the total activities of the brown fat using a Siemens Inveon microPET/CT scanner following injection with 250 Î¼Ci of 18F-Fluorodeoxyglucose via tail vein.
Lack of TRPV1 significantly decreased the expression of several genes that are implicated in lipolysis and thermogenesis in mice that were fed normal chow diet (NCD). Also, high fat diet caused a more significant down-regulation of thermogenic proteins in the adipose tissues of TRPV1-/- compared to wild type mice. Analyses of locomotion activity revealed that NCD-fed TRPV1-/- mice exhibited less activity compared to wild type mice. Consistently, thermogenesis was suppressed to a higher extent in HFD-fed TRPV1-/- mice compared to wild type mice.
Our data reveal that lack TRPV1 strikingly increases metabolic impairment compared to wild type mice. This suggests that the expression and activation of TRPV1 will help in shedding new light into a strategy to counteract obesity.