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Background: Diabetic kidney disease is a major cause of global end-stage renal diseases. Ectopic lipid deposition in the renal tissues of diabetic kidney disease is one major factor leading to renal fibrosis and chronic kidney disease. Pterostilbene has been reported to display lipid-lowing activity and participate in many kidney diseases. However, the influence of pterostilbene on the ectopic lipid deposition is unclear. We intend to explore the influence of pterostilbene on the ectopic lipid deposition in the kidneys of mice induced by high fat. Methods: A high-fat diet-induced diabetic mouse model was established to detect the alleviative effect of pterostilbene on the ectopic lipid deposition in the kidneys of diabetic mice. A biochemical analysis was performed to examine the levels of urine albumin, urine creatinine, serum creatinine, and blood urea nitrogen in mice after pterostilbene treatment. Histological analysis was conducted to detect the degree of renal injury and fibrosis. Oil red O staining and immunohistochemical staining were carried out to evaluate lipid droplets and the expression of adipose differentiation-related protein in renal tissues of the mice treated by pterostilbene. The protein levels were assessed by Western blotting. Results: Pterostilbene inhibits the expression of the TGF-β1 and p-smad3 and suppresses the protein levels of SREBP-1 and FAS, and it ultimately reduces the ectopic lipid deposition, alleviates the renal tubular damage and renal fibrosis in the kidneys of diabetic mice induced by high fat, and improves kidney function. Conclusion: Pterostilbene alleviates renal fibrosis and ectopic lipid deposition in the kidneys of diabetic mice induced by high-fat diet by inhibiting the TGF-β1/smad3 signaling. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) correlates with the high intake of fructose‐rich soft drinks. Both inflammation and dysregulated iron metabolism are pathogenic factors in the development of NAFLD. The present investigation assessed the effects of a high‐fructose diet (HF diet) on inflammation and iron metabolism. In this study, rats were fed a control or HF diet for 4, 8, or 12 weeks, after which insulin resistance, transaminases levels, serum and liver lipid profiles, inflammatory factors, and iron metabolism‐related molecules were evaluated. The activities of the hepatic inflammation‐associated pathways, IKKβ/NF‐κB, and JAK2/STAT3, were detected by western blot. Result showed that the HF diet‐fed animals developed a time‐dependent serum lipid increase and hepatic lipid accumulation as well as insulin resistance. Serum iron (SI), serum ferritin (SF), and transferrin saturation (TS) decreased while total iron‐binding capacity (TIBC) and serum transferrin (s‐TF) increased at 8 and 12 weeks in the HF diet group. The HF diet led to increased transaminases levels at 8 and 12 weeks, and iron deposition was observed in the liver, accompanied by an upregulation of ferritin light chain (FTL), hepcidin (HEPC), transferrin (TF), transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1), hemojuvelin (HJV), and divalent metal transporter 1 (DMT1). Moreover, ferroportin (FPN1) levels were downregulated, as expected from the increased HEPC. A progressive inflammation phenotype was apparent, with increased inflammatory factors, MDA, IL‐1β, IL‐6, and TNF‐α, in the serum and liver tissue. Concomitantly, the hepatic IKKβ/NF‐κB and JAK2/STAT3 pathways were activated. In summary, we verified that HF diet induces systemic iron deficiency and hepatic iron accumulation, likely due to the activation of inflammation via the NF‐κB and JAK2/STAT3 pathways. Practical applications: As increasing numbers of individuals consume HF diets, the health implications of this type of over nutrition become globally relevant. Using a high‐fructose diet rat model, our present study reveals inflammation as the link between a HF diet and dysregulated iron metabolism. Importantly, both inflammation and disrupted iron metabolism have been shown to be pathogenic factors in nonalcoholic fatty liver disease (NAFLD). The iron regulatory hormone, HEPC, is a link between the liver, inflammation, and iron metabolism. As fructose‐rich foods become increasingly abundant and people's fructose intake increases, the impact of high fructose on health requires increased attention. Little research has been conducted on the effects of fructose on iron metabolism. Our study provides useful insights into the prevention and treatment of iron metabolism disorders arising from metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objectives: Liraglutide, a well-established drug for treating diabetes mellitus (DM), has recently gained attention for its cardiovascular benefits in diabetes via multiple cellular activities; however, whether liraglutide improves myocardial damage by inhibiting pyroptosis and the mechanisms of these potential effects remain unknown., Materials and Methods: In this study, high-fat diet feeding and low-dose streptozotocin (STZ) injection were used to construct a rat DM model. Rats with fasting blood glucose (FBG) levels >16.7 mmol/l received subcutaneous injections of liraglutide (0.2 mg/kg) for 4 weeks. Metabolic parameters, the heart weight/body weight (HW/BW) ratio, and histopathology were examined. Protein levels of inflammatory, pyroptosis, and NOD-like receptor protein 3 (NLRP3) inflammasome markers were assessed via Western blotting. In in vitro studies, a sirtuin 1 (Sirt1) inhibitor (EX 527, 200 nM) and an AMP-activated protein kinase (AMPK) inhibitor (compound C, 20 µM) were used to inhibit Sirt1 and AMPK pathways, respectively., Results: Liraglutide significantly attenuated cardiac hypertrophy, pathological changes, inflammation, pyroptosis, and NLRP3 inflammasome activation, accompanied by increased Sirt1 and AMPK activation. Consistent with the in vivo results, liraglutide attenuated high glucose (HG)-induced pyroptosis and NLRP3 inflammasome activation along with enhanced Sirt1 and AMPK activation. After blockade of Sirt1 and AMPK signaling, the protective effect of liraglutide was restrained. Notably, EX 527 abolished the stimulatory effect of liraglutide on Sirt1 and AMPK signaling, whereas compound C blunted AMPK signaling without affecting Sirt1 signaling., Conclusion: Liraglutide may protect against myocardial damage by activating the Sirt1/AMPK signaling pathways to inhibit cellular pyroptosis in DM., Competing Interests: No conflicts of interest have been declared by the authors.