Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity

Abstract

To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 +/- 1.3 vs. 7.5 +/- 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2-5 g/day of triglycerides, which would represent 0.7-1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels (P < 0.01) and a trend for decreased SREBP-1c mRNA (P = 0.06). Energy restriction in obese patients decreased plasma insulin (P < 0.05) and leptin (P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.

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

“…In line with this, we found a strong inverse relationship between expression of genes associated with DNL, and both BMI and adipocyte cell size. This is in agreement with previous studies where lower expression of FASN was seen in adipose tissue of obese individuals, despite this group having increased hepatic lipogenesis compared with the lean [13], and where lower expression of FASN was seen in adipose tissue of obese individuals irrespectively of diet [35]. Other studies have not found any clear evidence that DNL is more active in adipose tissue obtained from obese individuals [36], even following a high carbohydrate diet [12].…”

“…BMI and cell size, however, remained strongly [10,35]. Also, the increased hepatic DNL in obese individuals compared with lean is not accompanied by increases in adipose tissue lipogenic capacity [13]. Together with our results, this implies that lipogenic genes do not seem to be expressed in tandem in the liver and adipose tissue, and may even be regulated in a reciprocal fashion.…”

“…Nevertheless, it is clear that DNL does operate in human adipose tissue [10,11], although it is not the major pathway for fat deposition. Expression of several lipogenic genes, principally FASN, has been shown to be higher in smaller human adipocytes [12,13]. Recently, however, it has been proposed that increased energy intake and accumulation of body fat is linked to increased expression of the lipogenic gene FASN in adipose tissue [14].…”

Orchestrated downregulation of genes involved in oxidative metabolic pathways in obese vs. lean high-fat young male consumers

“…As previously described, subjects with established obesity have an increased hepatic lipogenesis, but decreased lipogenic activity in adipose tissue (10). It has been suggested that the dysregulation of glyceroneogenesis (GNG) in WAT is a causal factor for obesity (3) and that a reduction in the expression of PCK1 (a key enzyme for GNG) and G6P, improved insulin sensitivity and glucose metabolism in mice (2).…”

Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis

“…31 The major confounding factor seems to be the degree of insulin resistance. 32 The key issue is whether or not obesity (at least some form of obesity) may be associated to an increase in DNL through the regular consumption of high CHO meals in state of positive energy balance.…”