Wednesday, June 8, 2011

Resveratrol Attenuates Insulin Resistance - Now, We Know Why: Grape Skin Polyphenol Ameliorates Intramuscular Fat Deposition and Improves Mitochondrial β-oxidation in Rats on a High Fat Diet.

Image 1: Grapes - sugary super food
and source of resveratrol.
Despite the literal "flood" of studies on the myriad of effects high doses of the grape polyphenol, resveratrol, have on isolated cell cultures; little is known about the mechanism behind its ameliorative effect on various symptoms of the metabolic syndrome. Now, a recent study (Chen. 2011) from the Department of Endocrinology at the Huazhong University of Science and Technology in Wuhan, China, sheds some light onto these underlying biological processes.

In the paper, which was published in the prestigious medical Journal Metabolism, the authors report the effects of intragastric administration of 100mg/kg resveratrol [human equivalent ~16mg/kg, i.e. ~1.3g for an 80kg adult] to 8-week old SD rats being fat a high fat diet (59% fat, 20% carbohydrate, 21% protein) over a time course of 8 weeks. Compared to the control group that was fed a "low fat" standard chow, the animals in the high fat, no resveratrol (HF8) group exhibited "significantly increased" fasting insulin levels accompanied by singificantly decreased insulin sensitivity, with a 30% reduced muscle glucose uptake. Further analysis revealed intramuscular lipid accumulation. Also, ...
SIRT1 activity and expression of genes related to mitochondrial biogenesis were greatly declined, whereas the gene for lipid transportation, FAT/CD36, was upregulated (P < .05). Subsarcolemmal but not IMF mitochondria displayed lower CS [citric synthase], ETC [electron transport chain], and β-oxidation activities.
In other words, the upregulation of the FAT/CD36 gene induced a higher influx of fats into the muscle. Thus, to maintain energy balance / prevent fat deposition, the Intra-muscular beta-oxidation activity would have to be upregulated. This however was only the case in the resveratrol treated high fat diet group (HF8E):
RES treatment protected rats against diet-induced intramuscular lipid accumulation and IR [insulin resistance], increased SIRT1 activity and mitochondrial biogenesis, and reverted the decline in SS [sarcolemmal; means referring to the thin transparent homogeneous sheath enclosing a striated muscle fiber] mitochondrial CS [citric synthase] and ETC [electron trabsport chain] activities. Importantly, although expression of FAT/CD36 was increased (11%, P < .05), activities of SS mitochondrial β-oxidation enzymes were largely enhanced (41%~67%, P < .05).
So, with a smaller increase in the "fat influx gene", FAT/CD36, and the concurrent upregulation of the surrounding the muscle mitochondria, an improvement of the overall "fat influx vs. fat oxidation" ratio (cf. figure 1) appears to be the underlying mechanism behind the beneficial effects resveratrol has on diet induced metabolic disturbances in real world (not petri dish) scenarios.
Figure 1: Relative expression of FAT/CD36 (indicator of fat transport into muscle) and CPT1, MCAT, LCAD (indicators of mitochondrial beta-oxidation) of rats on a high fat diet and rats on a high fat diet supplemented with 100mg/kg resveratrol per day; data in percent of normal fed control group (data adapted from Chen. 2011)

Now, the dieters among you will probably ask themselves: Will this help me lose weight faster? Just by the results of this study, this question cannot be answered... I certainly hope that you do not expect to slim down on a fattening diet (for rats this is a high fat diet), this - that is 100% certain - won't happen no matter how much resveratrol you take. After all, it would require further studies, if the same effects occur in human beings on a calorie restricted diet. Preliminary data from other studies (cf. Baile. 2011 for references) would suggest that this could be the case, especially for dieters who have more fat to shed than just your common love-handles - or, in other words, the fatter, more insulin resistant and metabolically deranged you are, the more likely it appears that you could benefit from supplementing (i.e. not replacing) a well-planned diet and exercise regimen with appropriate (>1g/day) doses of resveratrol.