• BMB Reports
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• v.51 no.9
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• pp.429-436
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• 2018

Fructose in the form of sucrose and high fructose corn syrup is absorbed by the intestinal transporter and mainly metabolized in the small intestine. However, excess intake of fructose overwhelms the absorptive capacity of the small intestine, leading to fructose malabsorption. Carbohydrate response element-binding protein (ChREBP) is a basic helix-loop-helix leucine zipper transcription factor that plays a key role in glycolytic and lipogenic gene expression in response to carbohydrate consumption. While ChREBP was initially identified as a glucose-responsive factor in the liver, recent evidence suggests that ChREBP is essential for fructose-induced lipogenesis and gluconeogenesis in the small intestine as well as in the liver. We recently identified that the loss of ChREBP leads to fructose intolerance via insufficient induction of genes involved in fructose transport and metabolism in the intestine. As fructose consumption is increasing and closely associated with metabolic and gastrointestinal diseases, a comprehensive understanding of cellular fructose sensing and metabolism via ChREBP may uncover new therapeutic opportunities. In this mini review, we briefly summarize recent progress in intestinal fructose metabolism, regulation and function of ChREBP by fructose, and delineate the potential mechanisms by which excessive fructose consumption may lead to irritable bowel syndrome.

• Molecules and Cells
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• v.39 no.11
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• pp.797-806
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• 2016

Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. $LXR{\alpha}$ activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, $LXR{\alpha}$ activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, $LXR{\alpha}$ might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and $LXR{\alpha}$ activation enhanced these effects, suggesting $LXR{\alpha}$ mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes.

• The Journal of Korean Medicine
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• v.37 no.1
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• pp.62-76
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• 2016

Objectives: The goal of this study was to investigate the anti-lipogenic effects of Samhwangsasim-tang(SHT), Daehwanghwangryunsasim-tang(DHT) aqueous extract on HepG2 cells with palmitate. Materials and Methods: HepG2 cells treated with palmitate were used in this study as hepatic steatosis model. Cells were treated with different concentrations of SHT, DHT aqueous extract for 24 hours. Cell viability and cytotoxicity were analyzed by MTT assay. Expressions of Bcl-2, Bax, Survivin, P21, TGF-${\beta}1$, LXR-${\alpha}$, ChREBP, ACC1, SCD1 mRNA were determined by Real-time PCR. Apoptosis of cells was detected by ELISA and FACS. Expression level of caspase-3 was studied by Western blot. Lipid accumulation was indicated by Oil Red O staining. Results: SHT, DHT aqueous extract had no cytotoxicity, but decreased palmitate-induced lipid accumulation in HepG2 cells. SHT aqueous extract suppressed fatty acid synthesis by inhibiting LXR-${\alpha}$, ChREBP, SCD1 activation and increasing TGF-${\beta}1$ expression level. DHT aqueous extract also suppressed fatty acid synthesis by decreasing ChREBP expression and increasing TGF-${\beta}1$ expression. Apoptosis of lipid accumulated cells was increased by enhanced activities of P21, caspase-3 and inhibited expressions of Bcl-2, Survivin. Conclusions: These results suggest that SHT and DHT have an anti-lipogenic effects on lipid accumulation of hepatic cell. Also SHT and DHT have an efficacy to increase apoptosis of adipocyte without cytotoxicity. Therefore, SHT and DHT might have potential clinical applications for treatment of hepatic steatosis.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.629-640
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• 2023

Purpose: Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver which is not a result of excessive alcohol consumption. Its global prevalence was estimated to be approximately 32% in the years 1994-2019. More than half of obese individuals and patients with diabetes are reported to have NAFLD as a comorbidity. This study aimed to investigate the impact of the autumn olive (Elaeagnus umbellata Thunb.) berry on insulin resistance and steatosis in rats fed a high-fructose diet. Methods: Six-week-old Wistar rats were divided into four groups. The control group received a diet consisting of 65% corn starch, while the fructose and experimental groups were fed a diet comprising 65% fructose (FRU) and an FRU diet containing 0.5% (low-dose autumn olive berry group; LAO) or 1.0% (high-dose autumn olive berry group; HAO) ethanol extract of autumn olive berry, respectively, for 10 weeks. Results: The HAO group exhibited significantly lower blood glucose levels compared to the fructose-fed group. Both the LAO and HAO groups showed a substantial reduction in serum insulin levels and insulin resistance when compared to the fructose-fed group. The consumption of LAO and HAO significantly ameliorated dyslipidemia and reduced the levels of triglycerides in the liver compared to the fructose-fed group. Additionally, the consumption of HAO resulted in lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to the fructose group. The hepatic expression of the sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) was significantly reduced in the LAO and HAO groups compared to the fructose group. Conclusion: Autumn olive berries improved steatosis by ameliorating insulin resistance and down-regulating the lipogenesis proteins in rats fed on high fructose diet.

• Journal of Life Science
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• v.32 no.4
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• pp.318-324
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• 2022

PPARγ and C/EBPα are master adipogenic transcription factors (TFs) required for adipose tissue development. They control the induction of many adipocyte genes and the early phase of adipogenesis in the embryonic development of adipose tissue. Adipose tissue continues to expand after birth, which, as a late phase of adipogenesis, requires the lipogenesis of adipocytes. In particular, the liver and adipose tissues are major sites for de novo lipogenesis (DNL), where carbohydrates are primarily converted to fatty acids. Furthermore, fatty acids are esterified with glycerol-3-phosphate to produce triglyceride, a major source of lipid droplets in adipocytes. Hepatic DNL has been actively studied, but the DNL of adipocytes in vivo remains not fully understood. Thus, an understanding of lipogenesis and adipose expansion may provide therapeutic opportunities for obesity, type 2 diabetes, and metabolic diseases. In adipocytes, DNL gene expression is transcriptionally regulated by lipogenesis coactivators, as well as by lipogenic TFs such as ChREBP and SREBP1a. Recent in vivo studies have revealed new insights into the lipogenesis gene expression and adipose expansion. Future detailed molecular mechanism studies will determine how nutrients and metabolism regulate DNL and adipose expansion. This review will summarize recent updates of DNL in adipocytes and adipose expansion in terms of transcriptional regulation.