Anti-obesity mechanism

While not altogether desirable, it is not necessarily deleterious if drug treatment decreases fat digestion or absorption as well as cholesterol absorption. As described previously, this is the mechanism of action of the anti-obesity product alii . However, if decreased cholesterol absorption is due solely to decreased fat absorption, the efficacy is likely to be poor or highly variable and dependent on diet composition. The primary concern with this outcome is that fat-soluble vitamins will partition into the oil phase and be sequestered, reducing their absorption. 

Nisoli, E. and M. O. Carruba (2000). An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action. Obes Rev 1(2) 127-39. 

Fig. 1. Mechanism of the pleiotropic actions of the thiazolidinediones. Working via the PPAR-y receptor system in adipose tissue, the thiazolidinediones interrupt the pathogenic signaling between the expanded visceral adipose mass in obesity, which leads to improved insulin sensitivity in skeletal muscle and hver, enhanced pancreatic P-cell insulin secretion, and improved vascular endothelial function. The processes affected by the thiazolidinediones include redistribution of adipose stores, reduced circulating levels of FFA, diminished levels and tissue effects of cytokines (TNF-a), and increased circulating levels of the insulin-sensitizing, anti-atherogenic plasma protein adiponectin, which also arises from adipose tissue. The thiazohdinediones have also been shown to have direct effects in muscle and endothelial cells, which is likely to also contribute to some of their pharmacologic activity.

Numerous mechanisms have been suggested for how n-3 PUFAs may improve inflammation and adipocyte function. N-3 PUFAs may decrease adiposity, adipocyte size and macrophage infiltration, enhance the production of anti-inflammatory adi-pokines and cytokines, and reduce the production of pro-inflammatory adipokines and cytokines (Calder et al., 2009). Research suggests that the ability of n-3 PUFAs to normalize the concentrations of the adipokines leptin and adiponectin may be related to the role of n-3 PUFAs in adiposity and insulin sensitivity. Lombardo et al. (2007) used 2-month-old male Wistar rats to investigate the effects of FAs on adipokines. The diets consisted of a starch-rich control diet and two sucrose-rich diets (to induce obesity) where corn oil or fish oil were the fat sources (8% by weight) the intervention period lasted for 2 months. Plasma leptin and adiponectin levels in rats... 

---