Effect of diosgenin on metabolic dysfunction: Role of ERβ in the regulation of PPARγ

Wang, Xin; Li, Jun; Long, Zi; Sun, Quangui; Liu, Ying; Wang, Lele; Zhang, Xiaodi; Hai, Chen

doi:10.1016/j.taap.2015.09.015

Cited by 18 publications

(18 citation statements)

References 28 publications

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“…Taking into account our previous and present data, one may assume that in neuronal cells BP-3 stimulates RXRα/ERβ/GPR30 and inhibits RXRβ/RXRγ/ERα/PPARγ intracellular pathways. It has been documented that ERβ may downregulate ERα/PPARγ and disrupt RXRα/PPARγ signaling [ 45 ]. RXRα is an obligatory heterodimer partner of PPARγ as well as RXRβ/RXRγ [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Benzophenone-3 Impairs Autophagy, Alters Epigenetic Status, and Disrupts Retinoid X Receptor Signaling in Apoptotic Neuronal Cells

et al. 2017

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Benzophenone-3 (BP-3) is the most widely used compound among UV filters for the prevention of photodegradation. Population studies have demonstrated that it penetrates through the skin and crosses the blood-brain barrier. However, little is known about the impact of BP-3 on the nervous system and its possible adverse effects on the developing brain. We demonstrated that the neurotoxic effects of BP-3 were accompanied by the induction of apoptosis, as evidenced by apoptosis-related caspase-3 activation and apoptotic body formation as well as the inhibition of autophagy, as determined by the downregulation of autophagy-related genes, decreased autophagosome formation, and reduced LC3B-to-LC3A ratio. In this study, we showed for the first time that the BP-3-induced apoptosis of neuronal cells is mediated via the stimulation of RXRα signaling and the attenuation of RXRβ/RXRγ signaling, as demonstrated using selective antagonist and specific siRNAs as well as by measuring the mRNA and protein expression levels of the receptors. This study also demonstrated that environmentally relevant concentrations of BP-3 were able to inhibit autophagy and disrupt the epigenetic status of neuronal cells, as evidenced by the inhibition of global DNA methylation as well as the reduction of histone deacetylases and histone acetyl transferases activity, which may increase the risks of neurodevelopmental abnormalities and/or neural degenerations.

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Section: Discussionmentioning

confidence: 99%

Benzophenone-3 Impairs Autophagy, Alters Epigenetic Status, and Disrupts Retinoid X Receptor Signaling in Apoptotic Neuronal Cells

et al. 2017

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“…The 3T3-L1 cells were cultured and induced to adipogenic differentiation as we previously did. 43 Briefly, 3T3-L1 preadipocytes were cultured in DMEM containing 10% fetal calf serum (FCS) until the cells became confluent. Two days post confluence (Day 0), the cells were induced to adipogenic differentiation using DMI differentiation medium consisting of DMEM containing 10% fetal bovine serum (FBS), 0.5 mM isobutylmethylxanthine (IBMX), 1 μM dexamethasone (DEX) and 167 nM insulin for 2 days.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Wang

et al. 2017

Cell Death Differ

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Hepatocyte nuclear factor 1b (HNF1b) is a transcription factor belonging to the HNF family. We aimed to investigate the role of HNF1b in white adipocyte differentiation. The expression of HNF1b was reduced in white adipose tissue (WAT) of both diet-induced and genetic obese mice and decreased during the process of 3T3-L1 adipocyte differentiation. Downregulation of HNF1b enhanced 3T3-L1 adipocyte differentiation and upregulation of HNF1b inhibited this process. Upregulation of HNF1b inhibited peroxisome proliferator-activated receptor γ (PPARγ) and its target gene expression, while downregulation of HNF1b increased those genes expression. Overexpression of PPARγ suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. HNF1b can directly bind with the promoter of PPARγ in 3T3-L1 cells, which was decreased after adipogenic differentiation. HNF1b promoted apoptotic and autophagic cell death in early differentiated adipocytes through regulation of cell cycle progress and cell death-related factors, and thus inhibited the process of mitotic clonal expansion (MCE). HNF1b acted as an antioxidant regulator through regulating various antioxidant enzymes via binding with antioxidant response element. Oxidant treatment suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. Overall, our results suggest that HNF1b is a novel negative regulator of adipocyte differentiation through regulation of PPARγ signaling, MCE and redox state.

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“…Real-time PCR and western blot were performed as we previously did [21]. For PCR, primers used were shown in Supporting Table S1.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of hepatocyte nuclear factor 1b induces hepatic steatosis through DPP4/NOX1-mediated regulation of superoxide

Long

Cao

et al. 2017

Free Radical Biology and Medicine

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder that is closely associated with insulin resistance and type 2 diabetes. Previous studies have suggested that hepatocyte nuclear factor 1b (HNF1b) ameliorates insulin resistance. However, the role of HNF1b in the regulation of lipid metabolism and hepatic steatosis remains poorly understood. We found that HNF1b expression was decreased in steatotic livers. We injected mice with lentivirus (LV) expressing HNF1b shRNA to generate mice with hepatic knockdown of HNF1b. We also injected high fat (HF) diet-induced obese and db/db diabetic mice with LV expressing HNF1b to overexpress HNF1b. Knockdown of HNF1b increased hepatic lipid contents and induced insulin resistance in mice and in hepatocytes. Knockdown of HNF1b worsened HF diet-induced increases in hepatic lipid contents, liver injury and insulin resistance in mice and PA-induced lipid accumulation and impaired insulin signaling in hepatocytes. Moreover, overexpression of HNF1b alleviated HF diet-induced increases in hepatic lipid content and insulin resistance in mice. Knockdown of HNF1b increased expression of genes associated with lipogenensis and endoplasmic reticulum (ER) stress. DPP4 and NOX1 expression was increased by knockdown of HNF1b and HNF1b directly bound with the promoters of DPP4 and NOX1. Overexpression of DPP4 or NOX1 was associated with an increase in lipid droplets in hepatocytes and decreased expression of DPP4 or NOX1 suppressed the effects of knockdown of HNF1b knockdown on triglyceride (TG) formation and insulin signaling. Knockdown of HNF1b increased superoxide level and decreased glutathione content, which was inhibited by downregulation of DPP4 and NOX1. N-acetylcysteine (NAC) suppressed HNF1b knockdown-induced ER stress, TG formation and insulin resistance. Palmitic acid (PA) decreased HNF1b expression which was inhibited by NAC. Taken together, these studies demonstrate that HNF1b plays an essential role in controlling hepatic TG homeostasis and insulin sensitivity by regulating DPP4/NOX1mediated generation of superoxide.

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Effect of diosgenin on metabolic dysfunction: Role of ERβ in the regulation of PPARγ

Cited by 18 publications

References 28 publications

Benzophenone-3 Impairs Autophagy, Alters Epigenetic Status, and Disrupts Retinoid X Receptor Signaling in Apoptotic Neuronal Cells

Benzophenone-3 Impairs Autophagy, Alters Epigenetic Status, and Disrupts Retinoid X Receptor Signaling in Apoptotic Neuronal Cells

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Inhibition of hepatocyte nuclear factor 1b induces hepatic steatosis through DPP4/NOX1-mediated regulation of superoxide

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