Comparison of the expression and activity of the lipogenic pathway in human and rat adipose tissue

Abstract

Lipogenesis is considered less active in human than in rat adipose tissue. This could be explained by different nutritional conditions, namely high-carbohydrate (HCHO) diet in rats and high-fat (HF) diet in humans. Adipose tissue was sampled (postabsorptive state) in rats and humans receiving HCHO or HF diets, ad libitum fed humans, and obese subjects. We measured 1 ) mRNA concentrations of fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), sterol regulatory element binding protein 1c (SREBP-1c), and carbohydrate response element binding protein (ChREBP), 2 ) SREBP-1c protein, and 3 ) FAS activity. FAS, ACC1, ChREBP, and SREBP1-c mRNA concentrations were unaffected by diet in humans or in rats. FAS and ACC1 mRNA levels were lower in humans than in rats ( P Ͻ 0.05). FAS activity was unaffected by diet and was lower in humans ( P Ͻ 0.05). SREBP-1c mRNA concentrations were similar in rats and humans, but the precursor and mature forms of SREBP-1c protein were less abundant in humans ( P Ͻ 0.05). ChREBP mRNA concentrations were lower in humans than in rats. In conclusion, the lipogenic capacity of adipose tissue is lower in humans than in rats. This is not related to differences in diet and is probably explained by lower abundance

Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes

“…The body weight gain of normal subjects fed an excess energy intake (approximately 2.5 times energy expenditure, with the excess derived from carbohydrate) cannot be explained by the increase in liver lipogenesis, suggesting that significant de novo lipogenesis occurs in other tissues, most likely adipose tissue [5]. However, although the key enzymes of fatty acid synthesis are present in human adipose tissue, their contribution to whole-body lipogenesis is considered to be lower than that of the liver [6,7]. Feeding simple carbohydrates also substantially increases the activity of FASN [8], which is necessary for de novo synthesis of long-chain, saturated fatty acids from acetyl coenzyme A (CoA), malonyl CoA and NADPH [9].…”

“…The FASN inhibitor C75 acts both centrally to reduce food intake and peripherally to increase fatty acid oxidation [1,14], leading to reduced fat mass and resolution of fatty liver in mice [2] and chickens [15] with diet-induced obesity. Whether these effects also play a role in human obesity needs to be clarified, especially since adipose tissue lipogenic capacity and FASN expression have been shown to be lower in humans than in rodents [6]. In turkeys, FASN gene polymorphisms are associated with increased fat mass [16].…”

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

“…In vitro experiments in rats and human cells report increased DNL in large cells [5,6], whereas other rat studies have reported decreased insulin-enhanced DNL from glucose [7,8]. Caution should be exercised in extrapolating results from rat studies, as the lipogenic capacity of adipose tissue in humans is lower than in rats [9]. Nevertheless, it is clear that DNL does operate in human adipose tissue [10,11], although it is not the major pathway for fat deposition.…”

Metabolic interaction of dietary sugars and plasma lipids with a focus on mechanisms andde novolipogenesis

“…For example, Minehira et al (2004) have reported that the lipogenic enzymes fatty acid synthase and sterol regulatory element binding protein 1c are expressed in adipose tissue after carbohydrate overfeeding, while two other studies (Diraison et al 2002;Letexier et al 2003) indicate that the same genes are unaffected by high-carbohydrate diets. Further research is needed in this area to understand the regulation of DNL in the adipose tissue.…”