TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation

Stella Bernardi, Giorgio Zauli, Christos Tikellis, Riccardo Candido, Bruno Fabris, Paola Secchiero, Mark E. Cooper, Merlin C. Thomas

Research output: Contribution to journalArticle

Abstract

TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] has recently been shown to ameliorate the natural history of DM (diabetes mellitus). It has not been determined yet whether systemic TRAIL delivery would prevent the metabolic abnormalities due to an HFD [HF (high-fat) diet]. For this purpose, 27 male C57bl6 mice aged 8 weeks were randomly fed on a standard diet, HFD or HFD + TRAIL for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection. Body composition was evaluated; indirect calorimetry studies, GTT (glucose tolerance test) and ITT (insulin tolerance test) were performed. Pro-inflammatory cytokines, together with adipose tissue gene expression and apoptosis, were measured. TRAIL treatment reduced significantly the increased adiposity associated with an HFD. Moreover, it reduced significantly hyperglycaemia and hyperinsulinaemia during a GTT and it improved significantly the peripheral response to insulin. TRAIL reversed the changes in substrate utilization induced by the HFD and ameliorated skeletal muscle non-esterified fatty acids oxidation rate. This was associated with a significant reduction of pro-inflammatory cytokines together with a modulation of adipose tissue gene expression and apoptosis. These findings shed light on the possible anti-adipogenic and anti-inflammatory effects of TRAIL and open new therapeutic possibilities against obesity, systemic inflammation and T2DM (Type 2 DM).

Original languageEnglish
Pages (from-to)547-555
Number of pages9
JournalClinical Science
Volume123
Issue number9
DOIs
Publication statusPublished - Nov 2012

    Fingerprint

Keywords

  • Apoptosis
  • High-fat diet
  • Inflammation
  • Insulin resistance
  • Obesity
  • Treatment
  • Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bernardi, S., Zauli, G., Tikellis, C., Candido, R., Fabris, B., Secchiero, P., Cooper, M. E., & Thomas, M. C. (2012). TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation. Clinical Science, 123(9), 547-555. https://doi.org/10.1042/CS20120176