Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice

Zeng, Hongliang; Huang, Suling; Xie, Fang; Zeng, Limin; Hu, Youhong; Liu, Ying

doi:10.1038/aps.2014.147

Cited by 10 publications

(5 citation statements)

References 52 publications

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“…Several compounds have been used to increase fatty acid oxidation and therefore insulin sensitivity5 6 by the activation of the enzyme 5′-adenosine monophosphate-activated protein kinase (AMPK) 7. The increase of fatty acid oxidation prevents the accumulation of lipids in several organs, decreasing the lipotoxicity 8.…”

Section: Introductionmentioning

confidence: 99%

Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects

Guevara‐Cruz

Godinez-Salas

Sánchez‐Tapia

et al. 2020

BMJ Open Diab Res Care

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ObjectiveObesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity.Research design and methods45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of ≥30 and≤40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, the same variables were assessed including a serum metabolomic analysis, gut microbiota, and a skeletal muscle biopsy was obtained to study the gene expression of fatty acid oxidation.ResultsIn the present study, we show that the consumption of genistein for 2 months reduced insulin resistance in subjects with obesity, accompanied by a modification of the gut microbiota taxonomy, particularly by an increase in the Verrucomicrobia phylum. In addition, subjects showed a reduction in metabolic endotoxemia and an increase in 5′-adenosine monophosphate-activated protein kinase phosphorylation and expression of genes involved in fatty acid oxidation in skeletal muscle. As a result, there was an increase in circulating metabolites of β-oxidation and ω-oxidation, acyl-carnitines and ketone bodies.ConclusionsChange in the gut microbiota was accompanied by an improvement in insulin resistance and an increase in skeletal muscle fatty acid oxidation. Therefore, genistein could be used as a part of dietary strategies to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed.

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Section: Introductionmentioning

confidence: 99%

Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects

Guevara‐Cruz

Godinez-Salas

Sánchez‐Tapia

et al. 2020

BMJ Open Diab Res Care

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“…Activation of AMP-activated protein kinase (AMPK) and AKT (also known as protein kinase B, PKB) regulates lipid metabolism by stimulating fatty acid uptake and promoting energy use by increasing total cellular ATP content via glycolysis and oxidative phosphorylation control (Bellacosa et al, 1991;Lan and Du, 2015). In addition, AMPK stimulation has been reported to restore lipid metabolism disorder in ob/ob mice (Samovski et al, 2015;Zeng et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Perfluorooctanoic acid exposure alters polyunsaturated fatty acid composition, induces oxidative stress and activates the AKT/AMPK pathway in mouse epididymis

Pan

Sheng

et al. 2016

Chemosphere

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“…In the present study, gastrodin upregulated the phosphorylation levels of AMPK, Nrf2 and the expression of HO-1, which was consistent with the previous study aforementioned. Previous studies also reported that AMPK and Nrf2 can mediate fatty acid oxidation and reduce oxidative stress, respectively (47,48). The activation of AMPK/Nrf2 signaling was previously found to improve lipid metabolism and attenuated oxidative stress in renal tissues of mice with type 2 diabetes-induced nephropathy (25,49).…”

Section: Discussionmentioning

confidence: 91%

Gastrodin inhibits high glucose‑induced inflammation, oxidative stress and apoptosis in podocytes by activating the AMPK/Nrf2 signaling pathway

2021

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Diabetic nephropathy (DN) is a serious and common complication of type 1 and 2 diabetes. Gastrodin has been reported to suppress high glucose (HG)-induced inflammation and oxidative stress in vivo and in vitro. However, the effect of gastrodin on DN has not been fully elucidated. The present study aimed to investigate the underlying mechanism involved in the effect of gastrodin on podocyte injury caused by DN. Cell viability was evaluated using Cell Counting Kit-8 assay and secretion levels of TNF-α, IL-1β and IL-6 were measured using ELISA. The levels of malondialdehyde, activities of lactate dehydrogenase and superoxide dismutase were quantified using corresponding assay kits. Additionally, cell apoptosis was analyzed by TUNEL assay, whilst protein expressions related to inflammation, apoptosis and the 5'-AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were measured by western blot analysis. The results showed that gastrodin increased the viability of MPC5 cells following HG stimulation. Gastrodin also alleviated HG-induced inflammation, oxidative stress and apoptosis in MPC5 cells. Furthermore, gastrodin promoted activation of the AMPK/Nrf2 pathway in MPC5 cells. Treatment with the AMPK inhibitor, compound C, reversed the inhibitory effects of gastrodin on inflammation, oxidative stress and cell apoptosis. To conclude, treatment of MPC5 cells with gastrodin can attenuate HG-induced inflammation, oxidative stress and cell apoptosis by activating the AMPK/Nrf2 signaling pathway. Results from the current study suggest that gastrodin can be used as an effective therapeutic agent against HG-induced podocyte injury in DN.

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Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice

Cited by 10 publications

References 52 publications

Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects

Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects

Perfluorooctanoic acid exposure alters polyunsaturated fatty acid composition, induces oxidative stress and activates the AKT/AMPK pathway in mouse epididymis

Gastrodin inhibits high glucose‑induced inflammation, oxidative stress and apoptosis in podocytes by activating the AMPK/Nrf2 signaling pathway

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