Regulation of Apelin-13 on Bcl-2 and Caspase-3 and Its Effects on Adipocyte Apoptosis

Objective. The effects of apelin-13 on the expression of Bcl-2 and caspase-3 factors and the apoptosis of adipocytes were studied at the cellular and animal levels. Methods. 3T3-L1 preadipocytes were cultured and grouped. The third-generation cells were added to the control DMSO solvent and amidation-modified apelin-13. The expression of Bcl-2 and caspase-3 were detected. The cell growth viability and cell apoptosis were detected. DOI model rats were established. The effects of apelin-13 on DOI rat biochemical indicators, the expression of Bcl-2, caspase-3, and cell apoptosis were investigated by injecting amidation-modified apelin-13 through the tail vein. Result. In in vitro experiments, amidation-modified apelin-13 can significantly reduce the growth viability of adipocytes and the expression of Bcl-2, increase the expression of caspase-3, and promote the apoptosis of adipocytes. Animal experiments also show that apelin-13 modified by amidation can adjust the abnormal biochemical indicators of DOI rats, decrease the expression of Bcl-2 in adipose tissue, increase the expression of caspase-3, and promote the apoptosis of adipocytes. Conclusion. Amidation of apelin-13 can promote fat cell apoptosis and reduce the incidence of obesity. The mechanism may be accomplished by inhibiting Bcl-2 and caspase-3 factors. This study helps us understand the effect of apelin-13 on fat cell apoptosis and hopes to provide a basis for the development of antiobesity drugs.

Metabolic and Epigenetics Action Mechanisms of Antiobesity Medicinal Plants and Phytochemicals

Ever-growing research efforts are demonstrating the potential of medicinal plants and their phytochemicals to prevent and manage obesity, either individually or synergistically. Multiple combinations of phytochemicals can result in a synergistic activity that increases their beneficial effects at molecular, cellular, metabolic, and temporal levels, offering advantages over chemically synthesized drug-based treatments. Herbs and their derived compounds have the potential for controlling appetite, inhibiting pancreatic lipase activity, stimulating thermogenesis and lipid metabolism, increasing satiety, promoting lipolysis, regulating adipogenesis, and inducing apoptosis in adipocytes. Furthermore, targeting adipocyte life cycle using various dietary bioactives that affect different stages of adipocyte life cycle represents also an important target in the development of new antiobesity drugs. In this regard, different stages of adipocyte development that are targeted by antiobesity drugs can include preadipocytes, maturing preadipocytes, and mature adipocytes. Various herbal-derived active compounds, such as capsaicin, genistein, apigenin, luteolin, kaempferol, myricetin, quercetin, docosahexaenoic acid, quercetin, resveratrol, and ajoene, affect adipocytes during specific stages of development, resulting in either inhibition of adipogenesis or induction of apoptosis. Although numerous molecular targets that can be used for both treatment and prevention of obesity have been identified, targeted single cellular receptor or pathway has resulted in limited success. In this review, we discuss the state-of-the-art knowledge about antiobesity medicinal plants and their active compounds and their effects on several cellular, molecular, and metabolic pathways simultaneously with multiple phytochemicals through synergistic functioning which might be an appropriate approach to better management of obesity. In addition, epigenetic mechanisms (acetylation, methylation, miRNAs, ubiquitylation, phosphorylation, and chromatin packaging) of phytochemicals and their preventive and therapeutic perspective are explored in this review.

Exacerbation of myopathy triggered by antiobesity drugs in a patient with multiple acyl-CoA dehydrogenase deficiency

Background Multiple acyl-CoA dehydrogenase deficiency (MADD) is a treatable lipid metabolism disorder that presents as myopathy and episodic metabolic crisis. The metabolic crisis is typically associated with prolonged fasting or physical stress; however, the mechanism of metabolic crisis is not yet fully understood. Case presentation A 28-year-old Taiwanese woman presented with dyspnoea, poor appetite, and muscle weakness after using antiobesity drugs, including metformin, triiodothyronine, and topiramate. MADD was diagnosed, and her symptoms rapidly improved after treatment with riboflavin, carnitine, and ubiquinone. To date, antiobesity drugs have not been reported to be a provoking factor in fatty acid oxidation disorder. Conclusions The increase of β-oxidation activity due to antiobesity drugs supports the hypothetical substrate competition model for MADD metabolic crisis. Because the drugs our patient used are commonly prescribed, we report this case to increase the vigilance and proactivity of clinicians in recognising this treatable adult-onset myopathy.

Neurochemical regulators of food behavior for pharmacological treatment of obesity: current status and future prospects

In recent decades, obesity has become a pandemic disease and appears to be an ultimate medical and social problem. Existing antiobesity drugs show low efficiency and a wide variety of side effects. In this review, we discuss possible mechanisms underlying brain–gut–adipose tissue axis, as well as molecular biochemical characteristics of various neurochemical regulators of body weight and appetite. Multiple brain regions are responsible for eating behavior, hedonic eating and food addiction. The existing pharmacological targets for treatment of obesity were reviewed as well.

Computational approaches for the discovery of natural pancreatic lipase inhibitors as antiobesity agents

Obesity is becoming one of the greatest threats to global health in the 21st century and therefore the development of novel antiobesity drugs is one of the top priorities of global drug research. An important treatment strategy includes the reduction of intestinal fat absorption through the inhibition of pancreatic lipase (PL). Natural products provide a vast pool of PL inhibitors with novel scaffolds that can possibly be developed into clinical products. Computational drug design methods have become increasingly invaluable in the drug discovery process. In recent years, the discovery of new antiobesity PL inhibitors has been facilitated by the application of computational methods. This review highlights some computer-aided drug design techniques utilized in the discovery of natural PL inhibitors.