|Image 1: Amorpha fruticosa (photo R. Ott) is a deciduous shrub growing to 4.5 m, the fruits of which contain about 500mg of amorfrutins per 1kg raw material.|
Glycyrrhiza foetida & Amorpha fruticosa amorfrutins - the future of blood sugar management?
With the so-called "amorfrutins" from the edible parts of the two legumes Glycyrrhiza foetida (roots) and Amorpha fruticosa (fruits), the former being related to the "licorice plant" Glycyrrhiza glaba and the latter a brush that is native to the east of the USA, a group of scientists from Germany and the UK have thus identified yet another potent plant-component that outperforms its synthetic competition pretty easily.
|Figure 1: Body weight (in g; left) and phosphorylated / non-phosphorylated PPAR-gamma (data from densitometric analyisis) of diet-induced obese mice on high fat diet (HFD) + placebo (vehicle), HFD + rosiglitazone or HFD + amorfrutin 1 (data adapted from Weidner. 2012)|
A note on the significance of PPAR-gamma phospohorylation: The phosphorylation of the peroxisome proliferator-receptor gamma is associated with a profound dysregulation of a large number of genes whose expression is altered in obesity. Its prevention is thus currently regarded as one of the most promising treatment strategies for insulin resistance; one that comes without the negative side-effect of increases in body weight for which all the other thiazolidinediones are notorious. It is therefore not surprising that the blockade of the phosphorylation of PPAR-gamma by amorfrutin 1 (the one denotes the first of the 4 amorfrutins the biological activity of which was investigated in the study) was "significantly correlated with improved insulin sensitivity" in the study at hand (Weidner. 2012).Other than in most synthetic selective PPAR-modulators, such as bezafibrate, for example, the weight loss was also not mediated by a reduction in food intake, but, as Weidner et al. speculate, a direct results of an increase in energy expenditure - a hypothesis that would certainly be supported by the slight, yet likewise statistically significant increase in thyroid hormone concentration (T4) in the amorfrutin group:
Because the complex effects of PPARγagonism on various endocrine systems and downstreamphysiological changes (e.g., change in thermogenesis, fatty acid oxidation, or activity) are not fully understood, it is difficult to probe all potential mechanisms by which the amorfrutins may affect weight regulation. For example, recent studies suggest that complex interaction of brain PPARγ-signaling with peripheral organs may contribute to the physio-logical regulation of energy balance (30, 31). Presumably, the amorfrutins as partial agonists may act on neuronal PPARγby an-tagonising diet-derived endogenous agonists such as fatty acids, thereby leading to relative weight loss.Against the background that we are apparently dealing with the PPAR equivalent to SERMs (selective estrogen receptor modulators such as clomid or tamoxifen) and SARMs (selective androgen receptor modulators), it appears prudent to mention that Weidner et al. did not find any cross-activities with other receptors, such as the estrogen receptors alpha and beta, the liver x receptor alpha, the constitutive androstane receptor, and the pregnane receptor. Cross-reactions like these are quite common with other xenobiotics (exogenous substances with biological effects that are produced by other organisms) and can lead to unexpected and mostly undesirable side effects (e.g. anti-androgen activity).
Leptin resistant? No problem for amorfrutins!
Contrary to rosgliatazone, the amorfrutins work their antidiabetic magic even in the presence of full-blown leptin resistance. While the former does not just fail to reduce, but actually promotes weight gain in leptin receptor-deficient db/db mice, treatment with amorfrutin 1...
[...] had no significant effects on mouse body weigh [... but] reduced plasma insulin concentrations more strongly than rosiglitazone (36% vs 19% decrease after 24 d) . Amorfrutin 1 treatment also decreased plasma concentrations of glucose, triglycerides, and free fatty acids. Possibly as a result of enhanced insulin sensitivity, amorfrutin 1 also appeared to prevent deterioration of pancreatic function in insulin-resistant mice, as pancreatic insulin levels improved compared to nontreated control mice.In genetically non-disadvantaged, normal diet-induced obese mice (DIO) and thus purportedly in most obese humans, treatment with amorfrutin 1 lead to identical reductions in the areas under the glucose and insulin curve in an intraperitoneal insulin sensitivity test (IPIST; is similar to an oral test, but the injection into the intraperitoneal cave ensures that 100% of the glucose actually hits the blood stream) and reduced the basal leptin levels to the same extend as rosiglitazone did (cf. figure 2).
|Figure 2: Areas under the glucose and insulin curve in an intraperitoneal insulin sensitivity test (left), basal leptin levels and photographs of the livers of the diet-induced obese mice at the end of the 24-day study period (data and images adapted from Weidner. 2012)|
- an increase of the PPAR-alpha dependent purported "anti liver-fat" co-factor Tbl1, and
- reduced inflammation in both the liver, as well as the white visceral adipose tissue of the rodents.
"When are we going to see those amor-thingies on the market?"
|Image 2: Amorfrutilean could be a weight loss adjuvant that works.|
If independent future human trials were yet able to confirm the previously discussed results, I am still pretty confident that we are soon going to see the supplement industry jumping aboard. With Amorfrutiburn, Amorfrutilean or Amorfrutibol being the most likely candidates for the BB.COM topselling "fat burners", weight loss adjuvants or "nutrient partitioners", respectively. And you know what, combined with a couple of lifestyle changes, this stuff could actually work - at least for the chubbier one's among the soon-to-be physical culturist. Whether leaner folks or even bodybuilders will benefit to the same extend does yet remain to be seen.