Effects of TNF-α antagonist infliximab on fructose-induced metabolic syndrome in rats

Abstract

Public health issues have been raised regarding fructose toxicity and its serious metabolic disorders. Deleterious effects of high fructose intake on insulin sensitivity, body weight, lipid homeostasis have been identified. The new millennium has witnessed the emergence of a modern epidemic, the metabolic syndrome (MS), in approximately 25% of the world’s adult population. The current study aimed to investigate the effect of the TNF-α antagonist infliximab on fructose-induced MS in rats. Rats were administered fructose (10%) in drinking water for 12 weeks to induce the experimental MS model. infliximab (5 mg/kg) was injected once weekly intraperitoneally starting on the 13th week for 4 weeks. Increase in body weight, blood glucose level, serum triglycerides (TGs), adiponectin level and blood pressure were present in MS rats. They also prompted increases in serum of leptin, TNF-α, and malondialdehyde (MDA) levels. Treatment with infliximab did not affect body weight, hyperglycemia or hypertension, but decreased serum TGs and increased serum HDL-c levels. Infliximab also decreased adiponectin levels. Surprisingly, infliximab increased MDA above its value in the MS group. These results reflect the fact that infliximab affects the manifestations of MS in rats. Though infliximab reduced TGs, increased HDL-c levels, reversed adiponectin resistance occurred by fructose, the drug failed to combat MS-mediated hyperglycemia, hypertension, and elevated MDA above the insult.

Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review)

“…Moreover, infliximab seems to ameliorate TNF-α-induced IR, in 3T3-L1 adipocytes, in vitro , by improving the insulin signaling pathway, via inhibition of protein tyrosine phosphatase 1B ( 341 ). Additionally, Abdelhamid et al ( 342 ) showed that infliximab administration in rats reduces TGs, increases HDL-c levels and reverses fructose-induced adiponectin resistance. Therefore, the authors suggested that infliximab may affect the manifestation of MetS.…”

“…Therefore, the authors suggested that infliximab may affect the manifestation of MetS. However, infliximab failed to affect MetS-mediated hyperglycemia, hypertension and the elevated peroxidation levels, as the levels of malondialdehyde dictate ( 342 ). Bernstein et al ( 343 ) investigated the effects of the inhibition of TNF-α with entanercept (a TNF-α blocker), in patients with MetS, for a 4-week treatment period.…”

Impact of a long‐term high‐fructose diet on systemic metabolic profiles of mice

“… 18 To the best of our knowledge, the majority of metabolomics studies on the effects of HFrD have focused on the analysis of urine and serum samples. 19 , 20 Thus, a systemic metabolomic analysis of high‐fructose‐influenced metabolic alterations is still lacking.…”

“…Moreover, targeted metabolomics analysis of serum samples from women consuming a high‐fructose diet revealed that high fructose intake in healthy women might lead to metabolic alterations in acylcarnitine and lysophosphatidylcholine via interruption of mitochondrial β‐oxidation and lipid peroxidation 18 . To the best of our knowledge, the majority of metabolomics studies on the effects of HFrD have focused on the analysis of urine and serum samples 19,20 . Thus, a systemic metabolomic analysis of high‐fructose‐influenced metabolic alterations is still lacking.…”