Thursday, June 16, 2011

Spicing Up Fat Loss: Structural Similarity to Melanocortin-4 Agonists Powers Piperine's (Black Pepper Extract) Fat Loss and Lipid Lowering Effects

Image 1: The molecular structure of
piperine makes it a potential
melanocortin-4 (MC4) agonist.
Despite the fact that the American fast food mentality has long conquered the Indian subcontinent, and obesity and diabetes are on a rise, the ideal of the curry eating, spicy food loving, lean Indian still figures in the minds of people in the "old" (Europe) and "new" world (America). Maybe this is part of the reason  why many of us willingly believe(d) in the ability of black pepper and other spice extract to literally "burn away" unwanted body fat, when we read about it in the latest supplement advertisement. Other than in the cases of Goji berries, Acai and co, a recent study (Shah. 2011) coming from, you guessed it, India, was not only able to confirm the validity of these claims (at least for rodents / more on that later), it also gives a reasonable explanation for the fat-burning effect of piper nigrum.

Using the standard rodent model of obesity-induced dyslipedemia (the high fat diet fet male Sprague Dawley rat), Shah et al. found that treatment with 40mg/kg (human equivalent dose: 6.5mg/kg)
significantly reduced not only body weight, triglyceride, total cholesterol, LDL, VLDL, and fat mass, but also increased the HDL levels, with no change in food intake.
In that, it is important to note, that both, weight loss, as well as the improvements in blood lipids occurred despite continuous intake of the fattening "high fat" diet (which was obviously also relatively high carb, just like the typical western diet), of which the rats kept eating about the same amount as before the initiation of treatment. A silbutramine treated control group, on the other hand, "exhibited a significant reduction in food intake as compared to the HFD-control group". In contrast to the prominent weight loss drug, piperine's effect on body weight, fat mass and blood lipids are thus not partly mediated by a simple reduction of caloric intake.
Figure 1: Epididymal (white adipose tissue, WAT) and interscapular (brown adipose tissue, BAT) fat mass in % of unsupplemented rats on a high fat diet (HFD) after administration of either sibutramine or piperine along with HFD for 11 weeks (data adapted from Shah. 2011)
In view of an unmistakable structural similarity of piperine to other selective melanocortin receptor agonists such as piperazine, piperidine, pyridazinone, tetrahydropyran, thiadazole, and diazole derivatives, the scientists propose direct melanocortin-4 receptor agonism at the level of the arcuate nucleus and thus "increased energy expenditure, and increased Insulin sensitivity" as an underlying mechanism for the anti-obesity, anti-hyperlipidemic effects of black pepper extract. Coupled with its thyrogenic activity, which "modulates apolipoprotein levels and insulin resistance" piperine turns out to be one of the few really promising fat loss adjuvants available on the vast supplement market.

To all that has been said, there is however one major caveat: Humans are not rodents, and whenever you read of thermogenic effects that have been observed in rats or mice, you must remember that human beings, other than those little critters lose most of their already negligible brown fat depots (BAT) within the first month of their lives. An organism lacking this type of thermogenic fat will obviously react very differently to compounds that speficitcally target thermogenic pathways. Whether the results from this study can be transfered to humans, or in other words, whether piperine will burn your love handles away, still warrants confirmation in human studies.

On a side note: The smaller reduction in BAT (cf. figure 1) observed in this study does not imply that the thermogenic effect of brown adipose tissue thermogenesis would not play a fundamental role in the metabolic effects of piperine. In order to raise the animal's body temperature, BAT actually uses white adipose tissue as a "fuel source".