SREBP-1c in nonalcoholic fatty liver disease induced by Western-type high-fat diet plus fructose in rats.
This study concentrated on the initial events triggering the development of nonalcoholic fatty liver disease induced by a high-fat plus fructose (HF-F) diet and on the possibility of delaying nonalcoholic fatty liver disease progression by adding dehydroepiandrosterone (DHEA) to the diet. Sterol regulatory element binding protein-1c (SREBP-1c) activation plays a crucial role in the progression of nonalcoholic fatty liver disease induced by an HF-F diet. This study investigated the protective effects of DHEA, a compound of physiological origin with multitargeted antioxidant properties, against the induction of SREBP-1c and on liver insulin resistance in rats fed an HF-F diet, which mimics a typical unhealthy Western diet. An HF-F diet, fortified or not with DHEA (0.01%, w/w), was administered for 15 weeks to male Wistar rats. After HF-F the liver showed unbalanced oxidative status, fatty infiltration, hepatic insulin resistance, and inflammation. The addition of DHEA to the diet reduced both activation of oxidative-stress-dependent pathways and expression of SREBP-1c and partially restored the expression of liver X-activated receptor-alpha and insulin receptor substrate-2 genes. DHEA supplementation of the HF-F diet reduced de novo lipogenesis and delayed progression of nonalcoholic fatty liver disease, demonstrating a relationship between oxidative stress and nonalcoholic fatty liver disease via SREBP-1c.
Aragno
Manuela
M
Department of Experimental Medicine and Oncology, University of Turin, 10125 Turin, Italy. manuela.aragno@unito.it
Tomasinelli
Chiara E
CE
Vercellinatto
Ilenia
I
Catalano
Maria G
MG
Collino
Massimo
M
Fantozzi
Roberto
R
Danni
Oliviero
O
Boccuzzi
Giuseppe
G
D000818:Animals; D016923:Cell Death; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology*; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005632:Fructose / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000473:pathology; D007333:Insulin Resistance; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
D004041:Dietary Fats; D051780:Sterol Regulatory Element Binding Protein 1; D005632:Fructose; D003687:Dehydroepiandrosterone