Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats

Abstract

<jats:p>We hypothesized that vitamin A (VA) status may affect obesity development. Male Zucker lean (ZL) and fatty (ZF) rats after weaning were fed a synthetic VA deficient (VAD) or VA sufficient (VAS) diet for 8 weeks before their plasma parameters and hepatic genes’ expression were analyzed. The body mass (BM) of ZL or ZF rats fed the VAD diet was lower than that of their corresponding controls fed the VAS diet at 5 or 2 weeks, respectively. The VAD ZL and ZF rats had less food intake than the VAS rats after 5 weeks. The VAD ZL and ZF rats had lower plasma glucose, triglyceride, insulin, and leptin levels, as well as lower liver glycogen content, net mass of epididymal fat, and liver/BM and epididymal fat/BM ratios (ZL only) than their respective VAS controls. VAD rats had lower hepatic Cyp26a1, Srebp-1c, Fas, Scd1, Me1, Gck, and Pklr (ZL and ZF); and higher Igfbp1 (ZL and ZF), Pck1(ZF only), and G6pc (ZF only) mRNA levels than their respective VAS controls. We conclude that ZL and ZF rats responded differently to dietary VA deficiency. VA status affected obesity development and altered the expression of hepatic genes for fuel metabolism in ZF rats. The mechanisms will help us to combat metabolic diseases.</jats:p>

SREBP: a novel therapeutic target

“…RA exists in multiple isomeric forms, such as all-trans RA and 9-cis RA [64]. It regulates gene expression through the activation of two families of nuclear receptors, RA receptors activated by all-trans RA and RXRs activated only by 9-cis RA [65,66].…”

Effects of individual and multiple fatty acids (palmitate, oleate and docosahaexenoic acid) on cell viability and lipid metabolism in LO2 human liver cells

“…With an increase in nutrient intake, the hepatic FA level is significantly increased, which may result in mitochondrial oxidation of FAs and oxidative stress in the liver (2,3), with subsequent development of metabolic disease. For example, diabetes is commonly associated with changes in hepatic glucose and lipid metabolism (4), which may be partly attributed to the altered expression levels of hepatic genes involved in glucose and lipid metabolism (5).…”

Vitamin A and Feeding Statuses Modulate the Insulin-Regulated Gene Expression in Zucker Lean and Fatty Primary Rat Hepatocytes

“…As anticipated [13]–[15], the food intake then started to decline until the end of the dietary manipulation. The two-day food intake of VAD-AD ZF rats quickly rose from ∼10 g initially to ∼60 g on days 17–18, leveled off between days 20 to 34, started to decline on days 35–36, reached ∼30 g on days 47–48, and leveled off again until the end of the dietary manipulation (right panel).…”

“…Rats fed a VAD diet after weaning reduced food intakes at around 5 weeks [13]. To determine how total and acute food intakes affect the insulin-regulated hepatic gene expression, an 8-week pair-feeding experiment was designed.…”

“…Two pair-feeding groups were set up to circumvent a potential caveat on the last day of pair-feeding. Since VAD animals consume significantly less diet than their VAS counterparts in ad libitum feeding condition [13]–[15], the VAS pair-fed rats would conceivably consume the last day's ration rapidly. This caveat would result in a fasting status in these rats and affect the analysis of insulin-regulated hepatic gene expression.…”