The TRPV1 channel regulates glucose metabolism.

Endocannabinoids (ECs) mediate effects via cannabinoid receptor types 1 and 2 (CB1 and 2) and transient receptor potential channel-vanilloid subfamily member 1 (TRPV1) channels. In high-fat diet (HFD)-induced obese mice overactivity of the EC system and inhibition of CB1 increase skeletal muscle glucose uptake. We explored the role of TRPV1. Male TRPV1+/+(WT) and TRPV1-/-(KO)-mice were fed (20 wk) a standard laboratory diet (SLD) or HFD. An 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 were 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 SB-366791. In EDL, fatty acid amide hydrolase (FAAH) mRNA was increased in KO vs. WT mice, irrespective of diet. Pyruvate dehydrogenase kinase isozyme 4 (PDK4) and mitochondrial uncoupling protein 3 (UCP3) were elevated and FA desaturase 2 (FADS2) mRNA lower in HFD mice, irrespective of genotype. CB1 and stearoyl-CoA desaturase 1 (SCD1) were lower in HFD WT mice only. In SOL, PDK4, UCP3, hormone-sensitive lipase (LIPE), fatty acid translocase (CD36), and carnitine palmitoyl transferase 2 (CPT2) were elevated and SCD1, FAAH, FADS2, and Troponin 1 (TNNC1) mRNA lower in HFD mice, irrespective of genotype. In conclusion, TRPV1 regulates glucose disposal in HFD mice. We propose that TRPV1 plays a role in coordinating glucose metabolism in EDL under conditions of metabolic stress.

The Effects of Vitamin D-Enriched Mushrooms and Vitamin D3 on Cognitive Performance and Mood in Healthy Elderly Adults: A Randomised, Double-Blinded, Placebo-Controlled Trial.

Despite abundant cross-sectional evidence that low vitamin D status is associated with risk of cognitive decline in ageing, interventional evidence for benefits of vitamin D supplementation is lacking. This study was a 6 month randomised, double-blinded placebo-controlled clinical trial of the effects of vitamin D3 (D3), enhanced vitamin D2 in a mushroom matrix (D2M), standard mushroom (SM) and placebo (PL) on cognition and mood in n = 436 healthy older male (49%) and female volunteers aged ≥ 60 years. Primary end points were change in serum vitamin D metabolites (25-OH-D, 25-OH-D2 and 25-OH-D3), cognitive performance, and mood over 24 weeks. Levels of total 25-OH-D and 25-OH-D3 were maintained in the D3 arm but decreased significantly (p < 0.05) in the remaining arms (D2M, SM and PL). Analysis also revealed differential changes in these metabolites depending on total vitamin D status at baseline. There were no significant effects of treatment on any of the measures of cognitive function or mood. Overall, the results show that daily supplementation of ~600 IU of vitamin D3 was sufficient to maintain 25-OH-D throughout winter months, but in contrast to existing cross-sectional studies there was no support for benefit of vitamin D supplementation for mood or cognition in healthy elderly people.

The expression of receptors for endocannabinoids in human and rodent skeletal muscle.

The endocannabinoid system is a lipid derived signalling system that has been shown to regulate appetite and energy metabolism. The most abundant endogenous endocannabinoid, anandamide, has been shown to activate the cannabinoid receptor type 1 (CB1) and type 2 (CB2) as well as the 'non-cannabinoid' transient receptor potential channel-vanilloid sub-family member 1 (TRPV1), before being rapidly metabolised by fatty acid amide hydrolase (FAAH). We have previously demonstrated the expression of CB1 and studied the effects of CB1 activation and inhibition in human skeletal muscle myotubes, however, not all results could be explained by CB1 mediated effects. This suggests that other receptors which are activated by endocannabinoids may be present in skeletal muscle. In this study we describe the presence of not only CB1, but also CB2, TRPV1 and the degrading enzyme FAAH in human and rodent skeletal muscle using reverse transcription polymerase chain reaction (RT-PCR).

Whey protein isolate improves vitamin B12 and folate status in elderly Australians with subclinical deficiency of vitamin B12.

SCOPE: Whey protein isolate (WPI) contains vitamin B12 and folate. However, the efficacy of WPI as a bioavailable source of these vitamins in the elderly with low vitamin B12 was not previously tested. We investigated the effects of WPI supplementation on vitamin B12 and folate status in blood and measured changes in homocysteine (HCY), methylmalonic acid (MMA), and genome integrity biomarkers in elderly individuals with low vitamin B12 status. The effect of WPI was compared to soy protein isolate (SPI). METHODS AND RESULTS: In this randomized controlled cross-over intervention trial, 56 subclinically vitamin B12 -deficient participants received 50 g WPI or 50 g SPI as a control for 8 wk followed by 16-wk washout phase and then cross-over to alternative supplement for next 8 wk. Consumption of WPI resulted in significant increase in serum active B12 (p < 0.0001) and serum folate (p = 0.0094). MMA, HCY, and nucleoplasmic bridges increased significantly after SPI intake but not after WPI (p = 0.052; p = 0.028; p = 0.0009, respectively). CONCLUSION: Results indicate that WPI consumption improves active B12 and folate status. Unlike SPI, WPI consumption may prevent increase in MMA, HCY, and genome instability in older Australians with low vitamin B12 status.

A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.

Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies.

The role of the endocannabinoid system in the regulation of energy expenditure.

Endocannabinoids, a lipid-derived signaling system, regulate appetite and motivation to eat via effects in the hypothalamus and nucleus accumbens. Not all the effects of endocannabinoids on fat mass can be explained by the regulation of food intake alone. Endocannabinoids and their receptors are located in areas of the central nervous system and multiple peripheral tissues involved in the regulation of intermediary metabolism and energy expenditure. In addition to regulating food intake by both central and peripherally mediated effects, endocannabinoids modify glucose and lipid metabolism so as to promote energy storage via lipogenesis and reduce energy expenditure. The endocannabinoid system appears to be overactive in obesity and may serve to maintain fat mass and underlies some of the metabolic consequences of obesity. Inhibition of the cannabinoid type-1 receptor ameliorates the effects of endocannabinoids on food intake and energy metabolism; lipogenesis is inhibited, lipolysis, fatty acid oxidation and glucose uptake increase.