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Article

Sulforaphane Prevents Hepatic Insulin Resistance by Blocking Serine Palmitoyltransferase 3-Mediated Ceramide Biosynthesis

1
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
2
Key Laboratory of Functional Dairy, Co-constructed by ministry of Education and Beijing Municipality, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
3
Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
4
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA
*
Author to whom correspondence should be addressed.
Received: 17 April 2019 / Revised: 22 May 2019 / Accepted: 23 May 2019 / Published: 27 May 2019
(This article belongs to the Special Issue The Role of Diet on Insulin Sensitivity)
Sulforaphane (SFA), a naturally active isothiocyanate compound from cruciferous vegetables used in clinical trials for cancer treatment, was found to possess potency to alleviate insulin resistance. But its underlying molecular mechanisms are still incompletely understood. In this study, we assessed whether SFA could improve insulin sensitivity and glucose homeostasis both in vitro and in vivo by regulating ceramide production. The effects of SFA on glucose metabolism and expression levels of key proteins in the hepatic insulin signaling pathway were evaluated in insulin-resistant human hepatic carcinoma HepG2 cells. The results showed that SFA dose-dependently increased glucose uptake and intracellular glycogen content by regulating the insulin receptor substrate 1 (IRS-1)/protein kinase B (Akt) signaling pathway in insulin-resistant HepG2 cells. SFA also reduced ceramide contents and downregulated transcription of ceramide-related genes. In addition, knockdown of serine palmitoyltransferase 3 (SPTLC3) in HepG2 cells prevented ceramide accumulation and alleviated insulin resistance. Moreover, SFA treatment improved glucose tolerance and insulin sensitivity, inhibited SPTLC3 expression and hepatic ceramide production and reduced hepatic triglyceride content in vivo. We conclude that SFA recovers glucose homeostasis and improves insulin sensitivity by blocking ceramide biosynthesis through modulating SPTLC3, indicating that SFA may be a potential candidate for prevention and amelioration of hepatic insulin resistance via a ceramide-dependent mechanism. View Full-Text
Keywords: sulforaphane; insulin resistance; glucose uptake; ceramide; liver sulforaphane; insulin resistance; glucose uptake; ceramide; liver
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MDPI and ACS Style

Teng, W.; Li, Y.; Du, M.; Lei, X.; Xie, S.; Ren, F. Sulforaphane Prevents Hepatic Insulin Resistance by Blocking Serine Palmitoyltransferase 3-Mediated Ceramide Biosynthesis. Nutrients 2019, 11, 1185. https://0-doi-org.brum.beds.ac.uk/10.3390/nu11051185

AMA Style

Teng W, Li Y, Du M, Lei X, Xie S, Ren F. Sulforaphane Prevents Hepatic Insulin Resistance by Blocking Serine Palmitoyltransferase 3-Mediated Ceramide Biosynthesis. Nutrients. 2019; 11(5):1185. https://0-doi-org.brum.beds.ac.uk/10.3390/nu11051185

Chicago/Turabian Style

Teng, Wendi, Yuan Li, Min Du, Xingen Lei, Siyu Xie, and Fazheng Ren. 2019. "Sulforaphane Prevents Hepatic Insulin Resistance by Blocking Serine Palmitoyltransferase 3-Mediated Ceramide Biosynthesis" Nutrients 11, no. 5: 1185. https://0-doi-org.brum.beds.ac.uk/10.3390/nu11051185

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