Melatonin ameliorates hepatic steatosis by inhibiting NLRP3 inflammasome in db/db mice

Yu, Y C; Chen, Dongru; Zhao, Ying‐Zheng; Zhu, Jianjun; Dong, Xiaohui

doi:10.1177/20587384211036819

Cited by 19 publications

(5 citation statements)

References 34 publications

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“…Hyperglycemia leads to various complications, including cirrhosis and eventually hepatocellular carcinoma [29]. Db/ db mice have consistently elevated levels of liver weight and liver glycogen [30,31], accompanied by liver steatosis, aggravated fbrosis [32]. Our results showed that T-fber could improve the liver weight compared with the model group.…”

Section: Discussionmentioning

confidence: 60%

T-Fiber, A Highland Barley Fiber-Rich Powder, Alleviates Hyperglycemia and Improves Kidney Pathology in Db/db Mice

Yang

Ma²,

Han³

et al. 2023

Journal of Food Biochemistry

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The role of dietary fiber in highland barley in lowering blood lipids has been continuously studied in recent years. However, its effects on diabetes and diabetic nephropathy are rarely studied. Considering that highland barley bran is rich in dietary fiber, the effective use of dietary fiber in highland barley bran can not only alleviate the symptoms of diabetes but also improve the local economy. This article aimed to study the effects of highland barley fiber-rich powder (T-fiber) with a high-quality natural dietary fiber ratio (insoluble fiber/soluble fiber = 3 : 1) on the symptoms of hyperglycemia in a diabetic mouse model. Compared with the model group’s blood glucose level (30.80 mmol/L), glucose tolerance (28.57 mmol/L), and glycosylated serum protein (2.43 mmol/L), T-fiber presented significant reductions in blood glucose (23.69 mmol/L), better glucose tolerance (21.32 mmol/L), and glycosylated serum protein (1.78 mmol/L) in the diabetic mouse model. Meanwhile, T-fiber effectively alleviated hepatocellular lesions. In addition, T-fiber not only improved kidney function by reducing the 24-hour urine output (8.25 ml), urine protein levels (11.51 mg), and serum creatinine (13.80 μmol/L) but also alleviated renal pathology, including glomerular hypertrophy, mesangial expansion, and fibrosis. The above results proved the ability of T-fiber to reduce blood glucose and alleviate liver and renal function in diabetic mice. Altogether, T-fiber is a capable formula for utilizing highland barley bran dietary fiber, which alleviates diabetes symptoms and endows highland barley with promising value.

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Section: Discussionmentioning

confidence: 60%

T-Fiber, A Highland Barley Fiber-Rich Powder, Alleviates Hyperglycemia and Improves Kidney Pathology in Db/db Mice

Yang

Ma²,

Han³

et al. 2023

Journal of Food Biochemistry

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“…In addition, the study made use of a genetic model of obesity and diabetes, which may differ from the human phenotype [ 37 ]. However, the homozygous diabetic leptin-resistant BKS.Cg-Dock7m+/+ Leprdb/J ( db/db ) mice model used here has been a useful tool in studies of liver dysfunction, as the animals have previously been shown to exhibit hepatic steatosis and lobular inflammation, along with significantly elevated alanine transaminase, aspartate aminotransferase, total cholesterol and triglyceride levels as compared with non-diabetic mice [ 38 , 39 ]. To address several of the highlighted limitations, the use of a high-fat, high-cholesterol diet model of hepatic steatosis in rodents may be beneficial.…”

Section: Discussionmentioning

confidence: 99%

Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db/db Mice

Mabasa

Kotze

Shabalala

et al. 2022

IJERPH

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of hepatic metabolic perturbations ranging from simple steatosis to steatohepatitis, cirrhosis and hepatocellular carcinoma. Currently, lifestyle modifications to reduce weight gain are considered the most effective means of preventing and treating the disease. The aim of the present study was to determine the therapeutic benefit of Sclerocarya birrea (Marula leaf extract, MLE) on hepatic steatosis. Obese db/db mice were randomly stratified into the obese control, metformin (MET) or MLE-treated groups. Mice were treated daily for 29 days, at which point all mice were euthanized and liver samples were collected. Hematoxylin and eosin staining was used for histological assessment of the liver sections, while qRT-PCR and Western blot were used to determine hepatic mRNA and protein expression, respectively. Thereafter, the association between methylenetetrahydrofolate reductase (Mthfr a key enzyme in one-carbon metabolism and DNA-methylation-induced regulation of gene transcription) and lipogenic genes was evaluated using Pearson’s correlation coefficient. Mice treated with MLE presented with significantly lower body and liver weights as compared with the obese control and MET-treated mice (p ≤ 0.05). Further, MLE treatment significantly inhibited hepatic steatosis as compared with the obese control and MET-treated mice (p ≤ 0.05). The reduced lipid accumulation was associated with low expression of fatty acid synthase (Cpt1; p ≤ 0.05) and an upregulation of the fatty acid oxidation gene, carnitine palmitoyltransferase (Cpt1; p ≤ 0.01), as compared with the obese control mice. Interestingly, MLE treatment improved the correlation between Mthfr and Cpt1 mRNA expression (r = 0.72, p ≤ 0.01). Taken together, the results suggest that Marula leaf extracts may inhibit hepatic steatosis by influencing the association between Mthfr and genes involved in hepatic lipid metabolism. Further studies are warranted to assess DNA methylation changes in lipid metabolism genes.

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“…Previous studies have shown that NLRP3 is expressed in a variety of cells and its mediated signaling pathway plays an important role in the progression of diabetes [ 35 , 36 ]. Several studies have shown that activation of NLRP3 can stimulate inflammatory formation and pyroptosis of cells [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

et al. 2021

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Diabetes mellitus is an important public health problem worldwide. Insulin deficiency caused by pancreatic β cell dysfunction is an important pathogenic factor of diabetes mellitus. This study evaluated whether empagliflozin (EMPA) protects the pancreas from diabetes mellitus-induced injury by downregulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/Gasdermin D (GSDMD) pyroptosis-related inflammasome pathway in vitro and in vivo. In vivo , animals were separated into blank control (control, C57/bl6j wild-type mice), diabetes model (db/db mice, BKS-Lepr em2Cd479 /Gpt mice), and db/db mice+EMPA (db/db+EMPA) groups. In vitro , pancreatic β cells were separated into low glucose (control), high glucose (HG), and HG+EMPA groups. The db/db+EMPA group were administered empagliflozin at 10 mg/(kg·day) by gavage for six months. Histological changes in the pancreatic tissues were observed by hematoxylin-eosin staining, and levels of the pyroptosis-related inflammatory factors NLPR3, caspase-1, and GSDMD were measured by immunohistochemistry and immunofluorescence staining methods. The Cell Counting Kit-8 assay was used to detect the effect of different concentrations of glucose and empagliflozin on the proliferation of mouse insulinoma islet β (β TC-6) cells. NLRP3/caspase-1/GSDMD expression was assessed by western blotting and immunofluorescent labeling in the β TC-6 cells. The results showed that empagliflozin reduced the pathological changes and inflammatory cell infiltration in the pancreatic tissues of db/db mice. Furthermore, empagliflozin not only reduced the expression levels of NLRP3/caspase-1/GSDMD in vitro , but also reduced their expression levels in vivo . In summary, our data suggested that empagliflozin protects the pancreatic tissues from diabetes mellitus-induced injury by downregulating the NLRP3/caspase-1/GSDMD pyroptosis-related inflammasome pathway.

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Melatonin ameliorates hepatic steatosis by inhibiting NLRP3 inflammasome in db/db mice

Cited by 19 publications

References 34 publications

T-Fiber, A Highland Barley Fiber-Rich Powder, Alleviates Hyperglycemia and Improves Kidney Pathology in Db/db Mice

T-Fiber, A Highland Barley Fiber-Rich Powder, Alleviates Hyperglycemia and Improves Kidney Pathology in Db/db Mice

Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db/db Mice

Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

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