Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet

• Published in: Journal of endocrinology Vol. 194; no. 3; pp. 539 - 550
• Main Authors: Barbuio, Raquel, Milanski, Marciane, Bertolo, Manoel B, Saad, Mário J, Velloso, Lício A
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.09.2007; Portland Press
• Subjects: Animals; Anti-Inflammatory Agents - therapeutic use; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Cytokines - metabolism; Dietary Fats - administration & dosage; Digestive system; Fatty Liver - drug therapy; Fatty Liver - metabolism; Fibrosis - drug therapy; Infliximab; Insulin - metabolism; Insulin Resistance; Liver - metabolism; Male; Medical sciences; Models, Animal; Pharmacology. Drug treatments; Rats; Rats, Wistar; Regular papers; Signal Transduction - drug effects; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - metabolism; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Pancreatic hormone; Rat; Digestive system; Liver; Rodentia; Insulin; Feeding; Steatosis; Signal transduction; Vertebrata; Mammalia; Infliximab; Diet; Animal
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/JOE-07-0234

Non-alcoholic fatty liver disease, induced by nutritional factors, is one of the leading causes of hepatic dysfunction in the modern world. The activation of proinflammatory signaling in the liver, which is induced by systemic and locally produced cytokines, and the development of hepatic insulin resistance are two important factors associated with the progression from steatosis to steatohepatitis, a pre-cirrhotic condition. The objective of the present study was to evaluate the effect of inhibition of tumour necrosis factor (TNF)-α , using the monoclonal antibody infliximab, on the expression of cytokines, induction of steatosis and fibrosis, and insulin signal transduction in the liver of Wistar rats fed a high-fat diet. Ten days of treatment with infliximab significantly reduced the expression of the proinflammatory markers, TNF-α , IL-6, IL-1β , and SOCS-3, in the liver of rats fed a high-fat diet. This was accompanied by reduced fat deposition and fibrosis and by improved insulin signal transduction through insulin receptor (IR)/IR substrate/Akt/FOXO1 and JAK2/STAT3 pathways. In conclusion, short-term inhibition of TNF-α with infliximab reduces inflammation and steatosis/fibrosis, while improving insulin signal transduction in an animal model treated with a high-fat diet.