DPP-4 Inhibition with Anagliptin Reduces Lipotoxicity-Induced Insulin Resistance and Steatohepatitis in Male Mice
ENDOCRINOLOGY
Authors: Sakai, Yuriko; Chen, Guanliang; Ni, Yinhua; Zhuge, Fen; Xu, Liang; Nagata, Naoto; Kaneko, Shuichi; Ota, Tsuguhito; Nagashimada, Mayumi
Abstract
Excessive hepatic lipid accumulation drives the innate immune system and aggravates insulin resistance, hepatic inflammation, and fibrogenesis, leading to nonalcoholic steatohepatitis (NASH). Dipeptidyl peptidase-4 (DPP-4) regulates glucose metabolism and is expressed in many different cell types, including the cells of the immune system. In addition, DPP-4 may be involved in macrophage-mediated inflammation and insulin resistance. This study investigated the effects of anagliptin (Ana), an inhibitor of DPP-4, on macrophage polarity and phenotype in the livers of mice with steatohepatitis. We investigated the effects of Ana on steatohepatitis induced via a high-cholesterol high-fat (CL) diet or a choline-deficient L-amino acid-defined, high-fat (CDAHF) diet. DPP-4 activity, liver histology, and insulin sensitivity were evaluated, and liver DPP-4(+) macrophages were quantified using fluorescence-activated cell sorting (FACS). Liver and plasma DPP-4 activity increased significantly in mice on both diets. FACS revealed that, compared with chow-fed mice, the CL-fed mice exhibited a significant increase in the proportion of DPP-4(+) liver macrophages, particularly the M1-type macrophages. Ana decreased hepatic lipid and M1 macrophage accumulation and stimulated M2 macrophage accumulation in the liver, thereby attenuating insulin resistance, steatohepatitis, and fibrosis. Importantly, Ana alleviated hepatic fibrosis and steatohepatitis in mice fed CL diet and CDAHF diet. Using Ana to inhibit DPP-4 reduced lipotoxicity-induced hepatic insulin resistance through regulating the M1/M2 macrophage status.
Light Intensity Effects on the Growth, Physiological and Nutritional Parameters of Tropical Perennial Legume Cover Crops
AGRONOMY-BASEL
Authors: Baligar, V. C.; Elson, M. K.; He, Z.; Li, Y.; Paiva, A. de Q.; Almeida, A. A. F.; Ahnert, D.
Abstract
In the early stages of the establishment of plantation crops such as cacao, perennial legume cover crops provide vegetative cover to reduce soil and nutrient loss by erosion. Light intensity at cover crop canopy levels greatly influences their adaptability and optimum growth. As tree crops mature, understory cover crops suffer from inadequate light intensity. A greenhouse experiment was undertaken with nine perennial legume cover crop species (Calopo, Ea-Ea, Jack Bean, Lab-Lab, Mucuna ana, Mucuna preta, Cowpea, Black Pigeon Pea and Mixed Pigeon Pea) to assess the effects of three photosynthetic photon flux densities (PPFDs, mu mol m(-2) s(-1)) 180 (inadequate light), 450 (moderate light) and 900 (adequate light) on growth, physiological and nutrient uptake parameters. PPFD had highly significant effects on leaf, shoot and root growth parameters and increasing the light intensity from 180 to 900 mu mol m(-2) s(-1) increased all growth parameters with the exception of specific leaf area. In all the legume cover crops, increasing the light intensity significantly increased the net assimilation rates (NAR), SPAD index and net photosynthesis (P-N) and its components, stomatal conductance (gs), transpiration (E) and vapor pressure deficit (VPD). Cover crop species, PPFD and their interactions significantly affected water flux (Vo) and various water use efficiency parameters (WUETOTAL, WUEINST and WUEINTR). Increasing the PPFD increased the WUE in all of the cover crops. Species and PPFD had highly significant effects on the uptake of macro- and micronutrients. Overall uptakes of all nutrients were increased with increases in the PPFD from 180 to 900 mu mol m(-2) s(-1). With few exceptions, the nutrient use efficiency (NUE) of the nutrients was significantly influenced by species, PPFD and their interactions. Except for Mn, increasing the PPFD from 180 to 900 mu mol m(-2) s (-1) increased the NUE for all the nutrients.