Anagliptin suppresses diet-induced obesity through enhancing leptin sensitivity and ameliorating hyperphagia in high-fat high-sucrose diet fed mice

Abstract

Obesity is a major risk factors for type 2 diabetes, and weight loss is beneficial to diabetic patients who are obese or overweight. Dipeptidyl peptidase-4 (DPP-4) inhibitors are anti-diabetic drugs. Although it has been known that the effect of most of the DPP-4 inhibitors on body weight is neutral, several studies suggested that some DPP-4 inhibitors suppressed body weight. Nonetheless, the mechanisms underlying DPP-4 inhibitor-induced weight loss are not fully understood. In this study, the mice fed high-fat high sucrose diet (HFHSD) containing a DPP4 inhibitor, anagliptin, showed reduced food intake and body weight compared to the mice fed non-treated HFHSD, but oxygen consumption and respiratory exchange ratio (RER) were not altered. Sequential administration of leptin suppressed food intake and body weight more apparently in anagliptin treated HFHSD fed mice than non-treated HFHSD fed mice. Oxygen consumption and RER were comparable between anagliptin treated and non-treated mice after leptin administration. The number of phospho STAT3 expressed cells in the arcuate nucleus after leptin administration was increased in anagliptin treated mice compared to non-treated mice. These data suggested that anagliptin ameliorated leptin resistance induced by HFHSD and thereby decreased food intake and body weight. These effects of anagliptin could be beneficial to the treatment of obese diabetic patients.

Phycocyanin Improves Reproductive Ability in Obese Female Mice by Restoring Ovary and Oocyte Quality

“…Recent research has shown that high-calorie diets can cause hyperphagia and promote obesity. Feeding obese mice with 2-fucosyllactose and anagliptin reduced both body weight and dietary intake (Kohno et al, 2020;Lee et al, 2020). We did observe increased body weights in mice fed a high-calorie diet, and reduced food consumption after PC gavage in obese mice, but PC administration did not reduce mouse body weight, illustrating that weight loss was not an effect of PC administration.…”

Anagliptin Protected against Hypoxia/Reperfusion-Induced Brain Vascular Endothelial Permeability by Increasing ZO-1

“…The molecular structure of anagliptin is shown in Figure . Anagliptin has shown promising antidiabetic properties in both clinical trials and animal experiments. , Recently, it was reported that the cytotoxicity and apoptosis induced by endogenous amyloid β in the neurons could be alleviated by anagliptin . Pronounced antioxidative stress effects have also been reported during the treatment of type II diabetes with anagliptin .…”

Efficacy of Dipeptidyl Peptidase-4 Inhibitors on Leptin in type 2 Diabetes Mellitus: A Meta-Analysis

“…Although the cardiovascular safety of DPP-4 inhibitors has been proven in T2DM, the net effect of these drugs on leptin concentrations in obesity-related disease remains unclear [24]. In Kitamura's study, leptin sensitivity was enhanced after anagliptin treatment in high-fat diet fed mice [25]. In the study evaluating the inhibitory effect of vildagliptin on brosis markers on white adipose tissue of high-fat diet-induced obese mice, vildagliptin prevents the increase of brosis markers and reduces leptin levels [26].…”