Objective. Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) commonly coexist and act synergistically to drive adverse clinical outcomes. This study is aimed at investigating the effects of exercise intervention and oral hypoglycaemic drug of metformin (MET) alone or combined on hepatic lipid accumulation. To investigate if oxidative stress and endoplasmic reticulum stress (ERS) are involved in lipotoxicity-induced hepatocyte apoptosis in diabetic mice and whether exercise and/or MET alleviated oxidative stress or ERS-apoptosis by AMPK-Nrf2-HO-1 signaling pathway. Methods. Forty db/db mice with diabetes (
random
blood
glucose
≥
250
mg
/
dL
) were randomly allocated into four groups: control (CON), exercise training alone (EX), metformin treatment alone (MET), and exercise combined with metformin (EM) groups. Hematoxylin-eosin and oil red O staining were carried out to observe hepatic lipid accumulation. Immunohistochemical and TUNEL methods were used to detect the protein expression of the binding immunoglobulin protein (BiP) and superoxide dismutase-1 (SOD1) and the apoptosis level of hepatocytes. ERS-related gene expression and the AMPK-Nrf2-HO-1 signaling pathway were tested by western blotting. Results. Our data showed that db/db mice exhibited increased liver lipid accumulation, which induced oxidative and ER stress of the PERK-eIF2α-ATF4 pathway, and hepatocyte apoptosis. MET combined with exercise training significantly alleviated hepatic lipid accumulation by suppressing BiP expression, the central regulator of ER homeostasis, and its downstream PERK-eIF2α-ATF4 pathway, as well as upregulated the AMPK-Nrf2-HO-1 signaling pathway. Moreover, the combination of exercise and MET displayed protective effects on hepatocyte apoptosis by downregulating Bax expression and TUNEL-positive staining, restoring the balance of cleaved-caspase-3 and caspase-3, and improving the antioxidant defense system to prevent oxidative damage in db/db mice. Conclusion. Compared to MET or exercise intervention alone, the combined exercise and metformin exhibited significant effect on ameliorating hepatic steatosis, inhibiting oxidative and ER stress-induced hepatocyte apoptosis via improving the capacity of the antioxidant defense system and suppression of the PERK-eIF2α-ATF4 pathway. Furthermore, upregulation of AMPK-Nrf2-HO-1 signaling pathway might be a key crosstalk between MET and exercise, which may have additive effects on alleviating hepatic lipid accumulation.
Low-angle lee-side slopes of dunes are commonly developed on the world’s riverbeds, and dune migration associated with sediment transport exert a major influence on riverine processes. However, the catenary-bead dune has been identified in the Yangtze River (YR) Estuary, featuring a higher lee-side angle. To date, the morphological variation and formation reasons of catenary-bead dunes in the YR Estuary remain uncharacterized. In this study, we used a multibeam echo system (MBES) to investigate the bedforms of the YR estuary during 2014–2015, as well as to discuss the seasonal variation of catenary-bead dunes. The results indicate that the catenary-bead dunes of the YR Estuary are characterized by growth during the flood season and extinction during the dry season. The lee-side angle is typically ~16.7°, which is larger than that of other dune types (3.7–8°) in the estuary; moreover, the catenary-bead dunes are higher than other dune types of the same length in the YR Estuary. The relationship between the dune height (H) and length (L) was found to be H = 0.1667L0.603 (R2 = 0.38), while the other dune types yielded the relationship of H = 0.0845L0.758 (R2 = 0.52). Strong runoff superimposing the ebb tide led to the development of catenary-bead dunes. Furthermore, the higher coarse sediment content (69.9–72%) and lower clay content (6.3–6.7%) of the riverbed sediment are favorable for their formation, while the higher curved crest-lines are favorable for the formation of the associated elliptical pits.
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