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Interleukin-6, but not tumour necrosis factor-alpha, 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.

SUBMITTER: Brass EP

PROVIDER: S-EPMC1137161 | biostudies-other | 1994 Jul

REPOSITORIES: biostudies-other

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Project description:AimTo determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes.MethodsThis test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks.ResultsPost-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve.ConclusionsControlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high-sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor α compared with basal insulin. The rise in post-meal glucose, but not triglycerides, significantly correlated with the rise in post-meal inflammatory and glycative biomarkers.

Project description:BackgroundThe humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha.AimsTo investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels.Study designCase-control study.MethodsSeventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay.ResultsWe observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05).ConclusionOur results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

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

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