Interleukin-6, but not tumour necrosis factor-α, increases lipogenesis in rat hepatocyte primary cultures

Abstract

The Kupffer-cell products interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) have been shown to stimulate hepatic lipogenesis in vivo. Studies were performed to define the direct effects of these cytokines on lipogenesis in primary-culture rat hepatocytes. Hepatocytes were cultured in the presence of IL-6 or TNF-alpha for periods of 24-72 h. IL-6 increased hepatocyte protein content per microgram of DNA. IL-6 also caused a dose- and time-dependent induction of hepatocyte capacity for incorporation of [2-14C]pyruvate into fatty acids (56% increase by 12.5 ng/ml IL-6 after 72 h of cytokine exposure). This increase in cellular lipogenic capacity was confirmed by using 3H2O incorporation into fatty acids as tracer. TNF-alpha did not increase hepatocyte lipogenesis. In contrast with studies in vivo, neither IL-6 nor TNF-alpha had any acute (2 h of exposure) effects on rates of lipogenesis. Both IL-6 and TNF-alpha are known to increase macrophage prostaglandin synthesis acutely. The prostaglandin E agonist misoprostol free acid (0.1 microM) acutely increased hepatocyte lipogenic rates by 14%. Thus, IL-6 can directly induce hepatocyte lipogenic capacity, and E-series prostaglandins can antagonize the acute inhibition of lipogenesis by glucagon. The observations provide further evidence for the role of Kupffer-cell products in the regulation of hepatocyte metabolism.

Circulating glucagon is associated with inflammatory mediators in metabolically compromised subjects

“…In this study, we describe the relationship between fasting glucagon and triglyceride concentrations in obese subjects, especially those that had shown IGT. These results are in line with glucagon infusion leading to decreased basal lipid oxidation and enhanced ability of insulin to inhibit lipid oxidation and augment lipid synthesis in classical studies in healthy subjects (36,37). However, IL6 also influenced lipid metabolism (38) and induced hypertriglyceridemia in experimental models.…”

Associations between liver 18F fluoro-2-deoxy-d-glucose accumulation and various clinical parameters in a Japanese population: influence of the metabolic syndrome

“…Kupffer cells are resident macrophages distributed along the liver sinusoid [10]. Kupffer cells of the liver can also secrete cytokines, including tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) [11]. Bioactive molecules generated by Kupffer cells and liver endothelial cells in response to varied stimuli have the capacity to contribute to the regulation of hepatic metabolism.…”

Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance

“…Kupffer cells of the liver can also secrete cytokines, and it has been found that factors such as TNF-␣ and IL-6 can influence fatty acid metabolism in the liver and dispose to formation of fatty liver (3,7,10). These inflammatory markers can also contribute to risk for CVD (26).…”