On a final note current study provides evidence for

On a final note current study provides evidence for potential anti-obesity activity of Hibiscus rosa sinensis flower fraction through activation of AMPK, which reduced pre-adipocyte differentiation to mature adipocytes. Further in vivo obesity studies need to be carried out to ascertain its anti-obesity efficacy and to evaluate its effect on insulin sensitivity.
Acknowledgements Current research work was funded and supported by Department of Science and Technology, Science and Engineering Research Board [SERB], Government of India, New Delhi [F. No.-SR/YS/LS-82/2013].
Introduction The fasudil plays an important role in the evaluation and control of energy homeostasis. Blood concentrations of glucose and fatty acids are sensed by neurons of the hypothalamus, which adjusts feeding behaviour and monitors fatty-acid metabolism. Several laboratories have attempted to design anti-obesity drugs and modulate fatty-acid metabolism to inhibit food intake. C75 is a synthetic inhibitor of fatty-acid synthase (FAS) [1] and has been proposed as an anti-obesity agent since its administration decreases food intake and body weight in rodents [2], [3], [4], [5]. C75 can alter the metabolism of neurons in the hypothalamus, where an increase in the level of malonyl-CoA due to FAS inhibition serves as a secondary messenger of nutrient status, thereby mediating the suppression of food intake [6], [7]. Hypothalamic levels of long-chain fatty acyl-CoA (LCFA-CoA) also signal nutrient availability and control food intake [8]. Malonyl-CoA signals the availability of lipid and carbohydrate fuels [9] and acts as a physiological inhibitor of the enzyme carnitine palmitoyltransferase 1 (CPT1). CPT1 catalyzes the first step in the transport of LCFA from the cytoplasm to the mitochondria, and is the rate-limiting step in β-oxidation. Mammalian tissues express three CPT1 isoforms: CPT1A, CPT1B and CPT1C which differ in their sensitivity to malonyl-CoA and tissue distribution [10], [11]. CPT1A and CPT1C are expressed in the brain. CPT1A is located in the mitochondrial membrane and CPT1C is expressed in the endoplasmic reticulum of neurons where although it has CPT1 activity, it does not participate in mitochondrial fatty-acid oxidation [12]. Interestingly, our group has generated a mutant form of CPT1A insensitive to malonyl-CoA (CPT1A M593S), and a mutant form of carnitine acetyltransferase (CrAT) that swaps its preference from short to LCFA-CoA (CrAT D356A/M564G). These mutants have allowed us to examine the structural requirements of substrates and inhibitors [13], [14], [15]. The inhibition of FAS by C75 produces an accumulation of malonyl-CoA which is difficult to reconcile with the activation of CPT1 reported by others [2], [16], [17], [18]. To unravel this paradox the mechanism of action of C75 needs to be examined. We recently demonstrated that C75 is converted in vitro to C75-CoA, a potent inhibitor of CPT1 [19]. CPT1 activity was also inhibited in mitochondria from pancreas-, muscle-, and kidney-derived cell lines incubated with C75, which indicates that C75-CoA is produced in these cells. This inhibition was followed by a decrease in fatty-acid oxidation. The role of CPT1 in heart, liver and pancreatic β-cells makes it a potential target in the treatment of diabetes, obesity, and other human diseases.