scholarly journals Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis

2020 ◽  
Vol 9 (9) ◽  
pp. 946-954
Author(s):  
Riying Liang ◽  
Meijun Wang ◽  
Chang Fu ◽  
Hua Liang ◽  
Hongrong Deng ◽  
...  
Keyword(s):  
Kidney Disease ◽  
High Fat Diet ◽  
Mesangial Cells ◽  
Morphological Changes ◽  
Kidney Injury ◽  
Sirtuin 1 ◽  
High Fat ◽  
Interacting Protein ◽  
Urine Albumin ◽  
Glucagon Like Peptide 1

Background: Obesity is associated with the development and progression of chronic kidney disease. Emerging evidence suggests that glucagon-like peptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (SIRT1) was considered as a crucial regulator in metabolism-related kidney disease. Herein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated. Methods: Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its protective effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mesangial cells was elucidated. Results: Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregulated, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxidative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV40 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the downregulation of TXNIP by liraglutide was blocked. Conclusions: Liraglutide might have a beneficial effect on metabolism-related kidney damage by inhibiting apoptosis via activation of SIRT1 and suppression of TXNIP pathway.

Silymarin protects against high fat diet-evoked metabolic injury by induction of glucagon-like peptide 1 and sirtuin 1

2019 ◽  
Vol 56 ◽  
pp. 136-144 ◽  
Author(s):  
Kai-Jyun Chang ◽  
Jer-An Lin ◽  
Sheng-Yi Chen ◽  
Ming-Hung Weng ◽  
Gow-Chin Yen
Keyword(s):  
High Fat Diet ◽  
Sirtuin 1 ◽  
High Fat ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

2038-P: Rice Endosperm Protein Intake in Childhood Suppresses the Development of High-Fat Diet-Induced Metabolic Disorders and Kidney Disease during Adulthood in Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2038-P
Author(s):  
YUKI HIGUCHI ◽  
MICHIHIRO HOSOJIMA ◽  
HIDEYUKI KABASAWA ◽  
SHOJI KUWAHARA ◽  
RYOHEI KASEDA ◽  
...  
Keyword(s):  
Kidney Disease ◽  
High Fat Diet ◽  
Protein Intake ◽  
Metabolic Disorders ◽  
High Fat ◽  
Rice Endosperm ◽  
Endosperm Protein

scholarly journals Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maki Murakoshi ◽  
Tomohito Gohda ◽  
Eri Adachi ◽  
Saki Ichikawa ◽  
Shinji Hagiwara ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Tubular Damage ◽  
Standard Diet ◽  
Mrna Levels ◽  
High Fat ◽  
Organ Specific

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.

scholarly journals Delayed Exercise Training Improves Obesity-Induced Chronic Kidney Disease by Activating AMPK Pathway in High-Fat Diet-Fed Mice

2020 ◽  
Vol 22 (1) ◽  
pp. 350
Author(s):  
Florian Juszczak ◽  
Maud Vlassembrouck ◽  
Olivia Botton ◽  
Thomas Zwakhals ◽  
Morgane Decarnoncle ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Exercise Training ◽  
High Fat Diet ◽  
Interstitial Fibrosis ◽  
Calorie Intake ◽  
Acid Oxidation ◽  
Obese Mice ◽  
High Fat ◽  
Ampk Pathway

Exercise training is now recognized as an interesting therapeutic strategy in managing obesity and its related disorders. However, there is still a lack of knowledge about its impact on obesity-induced chronic kidney disease (CKD). Here, we investigated the effects of a delayed protocol of endurance exercise training (EET) as well as the underlying mechanism in obese mice presenting CKD. Mice fed a high-fat diet (HFD) or a low-fat diet (LFD) for 12 weeks were subsequently submitted to an 8-weeks EET protocol. Delayed treatment with EET in obese mice prevented body weight gain associated with a reduced calorie intake. EET intervention counteracted obesity-related disorders including glucose intolerance, insulin resistance, dyslipidaemia and hepatic steatosis. Moreover, our data demonstrated for the first time the beneficial effects of EET on obesity-induced CKD as evidenced by an improvement of obesity-related glomerulopathy, tubulo-interstitial fibrosis, inflammation and oxidative stress. EET also prevented renal lipid depositions in the proximal tubule. These results were associated with an improvement of the AMPK pathway by EET in renal tissue. AMPK-mediated phosphorylation of ACC and ULK-1 were particularly enhanced leading to increased fatty acid oxidation and autophagy improvement with EET in obese mice.

scholarly journals Proximal tubular epithelial insulin receptor mediates high fat diet-induced kidney injury

JCI Insight ◽  
2021 ◽  
Author(s):  
Hak Joo Lee ◽  
Meenalakshmi M. Mariappan ◽  
Luke Norton ◽  
Terry Bakewell ◽  
Denis Feliers ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
High Fat Diet ◽  
Kidney Injury ◽  
High Fat ◽  
Proximal Tubular

scholarly journals Sex modulates hepatic mitochondrial adaptations to high-fat diet and physical activity

2019 ◽  
Vol 317 (2) ◽  
pp. E298-E311 ◽  
Author(s):  
Colin S. McCoin ◽  
Alex Von Schulze ◽  
Julie Allen ◽  
Kelly N. Z. Fuller ◽  
Qing Xia ◽  
...  
Keyword(s):  
Physical Activity ◽  
High Fat Diet ◽  
Wheel Running ◽  
Transcriptional Coactivator ◽  
High Fat ◽  
Respiratory Capacity ◽  
Interacting Protein ◽  
Low Fat Diet ◽  
The Impact ◽  
Mitochondrial Adaptations

The impact of sexual dimorphism and mitophagy on hepatic mitochondrial adaptations during the treatment of steatosis with physical activity are largely unknown. Here, we tested if deficiencies in liver-specific peroxisome proliferative activated-receptor-γ coactivator-1α (PGC-1α), a transcriptional coactivator of biogenesis, and BCL-2/ADENOVIRUS EIB 19-kDa interacting protein (BNIP3), a mitophagy regulator, would impact hepatic mitochondrial adaptations (respiratory capacity, H2O2production, mitophagy) to a high-fat diet (HFD) and HFD plus physical activity via voluntary wheel running (VWR) in both sexes. Male and female wild-type (WT), liver-specific PGC-1α heterozygote (LPGC-1α), and BNIP3 null mice were thermoneutral housed (29–31°C) and divided into three groups: sedentary-low-fat diet (LFD), 16 wk of (HFD), or 16 wk of HFD with VWR for the final 8 wk (HFD + VWR) ( n = 5–7/sex/group). HFD did not impair mitochondrial respiratory capacity or coupling in any group; however, HFD + VWR significantly increased maximal respiratory capacity only in WT and PGC-1α females. Males required VWR to elicit mitochondrial adaptations that were inherently present in sedentary females including greater mitochondrial coupling control and reduced H2O2production. Females had overall reduced markers of mitophagy, steatosis, and liver damage. Steatosis and markers of liver injury were present in sedentary male mice on the HFD and were effectively reduced with VWR despite no resolution of steatosis. Overall, reductions in PGC-1α and loss of BNIP3 only modestly impacted mitochondrial adaptations to HFD and HFD + VWR with the biggest effect seen in BNIP3 females. In conclusion, hepatic mitochondrial adaptations to HFD and treatment of HFD-induced steatosis with VWR are more dependent on sex than PGC-1α or BNIP3.

scholarly journals Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy

2018 ◽  
Vol 19 (12) ◽  
pp. 3903 ◽  
Author(s):  
Xiaofei Zhu ◽  
Jingyi Yang ◽  
Wenjuan Zhu ◽  
Xiaoxiao Yin ◽  
Beibei Yang ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Sirtuin 1 ◽  
Lipid Lowering ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
High Fat ◽  
Density Lipoprotein Receptor

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1—a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

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