Fish oil decreases hepatic lipogenic genes in rats fasted and refed on a high fructose diet

Abstract

Fasting and then refeeding on a high-carbohydrate diet increases serum and hepatic triacylglycerol (TAG) concentrations compared to standard diets. Fructose is a lipogenic monosaccharide which stimulates de novo fatty acid synthesis. Omega-3 (n-3) fatty acids stimulate hepatic β-oxidation, partitioning fatty acids away from TAG synthesis. This study investigated whether dietary n-3 fatty acids from fish oil (FO) improve the hepatic lipid metabolic response seen in rats fasted and then refed on a high-fructose diet. During the post-prandial (fed) period, rats fed a FO rich diet showed an increase in hepatic peroxisome proliferator-activated receptor α (PPAR-α) gene expression and decreased expression of carbohydrate responsive element binding protein (ChREBP), fatty acid synthase (FAS) and microsomal triglyceride transfer protein (MTTP). Feeding a FO rich diet for 7 days prior to 48 h of fasting resulted in lower hepatic TAG, lower PPAR-α expression and maintenance of hepatic n-3 fatty acid content. Refeeding on a high fructose diet promoted an increase in hepatic and serum TAG and in hepatic PPAR-α, ChREBP and MTTP expression. FO did not prevent the increase in serum and hepatic TAG after fructose refeeding, but did decrease hepatic expression of lipogenic genes and increased the n-3 fatty acid content of the liver. n-3 Fatty acids can modify some components of the hepatic lipid metabolic response to later feeding with a high fructose diet.

Figure 1

Fed state (post-prandial) parameters of rats fed a control (C) or fish oil (FO) diet for 7 days. (A) Serum triacylglycerol (TAG); (B) serum total cholesterol; (C) serum HDL cholesterol; (D) serum non-esterified fatty acids (NEFA); (E) liver weight as a percentage of body weight; (F) hepatic TAG; (G) hepatic total cholesterol; (H) hepatic content of fatty acid synthase; (I) hepatic fatty acid profile; (J) hepatic gene expression. PPAR-α—Peroxisome proliferator-activated receptor α; SREBP-1c—sterol regulatory element binding protein-1c; ChREBP—carbohydrate responsive element binding protein; FAS—fatty acid synthase; MTTP—microsomal triglyceride transfer protein. * Indicates significantly different from control (p < 0.05).

Figure 2

Fasting state parameters of rats fed a control (FC) or fish oil (FFO) diet for 7 days prior to a 48 h fast. (A) Serum triacylglycerol (TAG); (B) serum total cholesterol; (C) serum HDL cholesterol; (D) serum non-esterified fatty acids (NEFA); (E) liver weight as a percentage of body weight; (F) hepatic TAG; (G) hepatic total cholesterol; (H) hepatic content of fatty acid synthase; (I) hepatic fatty acid profile; (J) hepatic gene expression (see Figure 1 for abbreviations). * Indicates significantly different from control (p < 0.05).

Figure 3

Parameters of rats refed on a control or a high-fructose diet after 7 days of feeding a control or fish oil diet and then 48 h of fasting. (A) serum triacylglycerol (TAG); (B) serum total cholesterol; (C) serum HDL cholesterol; (D) serum non-esterified fatty acids (NEFA); (E) liver weight as a percentage of body weight; (F) hepatic TAG; (G) hepatic total cholesterol; (H) hepatic content of fatty acid synthase; (I) hepatic gene expression (see Figure 1 for abbreviations). RC—refed control group; FORC—fish oil refed control group; RFr—refed fructose group; FORFr—fish oil refed fructose group. Bars with the same letter are not significantly different (p < 0.05) by Tukey’s test (^a,b,c).