Toll-like receptor signaling in adipose tissue development

Abstract

Toll-like receptor (TLR) is a family of pattern-recognition receptor proteins responsible for triggering inflammatory responses for innate immune defense. By detecting ligands that are commonly found as microbial structural components, TLRs induce the production of inflammatory cytokines and alteration of metabolic responses via transcriptional activation. Its signaling participates in the endocrine control of adipose tissue, in both settings of healthy physiology and pathological development of obesity. Adipose tissue (AT) is developed as a highly plastic reservoir organ to store and release nutrients in case of nutrient excess and insufficiency. Its structure and secretory function is remodeled to adapt to chronic excess of nutrients when obesity develops. Previous studies mainly focused on the role of TLR signaling in individual inflammatory or metabolic responses. In this study, it was targeted to reveal the overall participation of TIR-domain-containing adaptor-inducing interferon-β (TRIF), a downstream TLR cytosolic adaptor, in adipose tissue remodeling. Trif-/- mice fed with normal Chow diet for 10 weeks exhibited shrinkage in visceral fat (VF) tissue, as well as the reduction in adipocyte size, compared to wild-type (WT) control. The observation was associated with an insignificant trend of elevated adipogenic gene expression in VF under TRIF deficiency. Cidec, a protein responsible for adipocyte enlargement, showed a significantly reduced protein expression in Trif-/- small VF adipocytes in situ. These observations were independent of angiogenesis in VF. The total cholesterol and triglyceride levels in Trif-/- mice in plasma, liver, muscle, pancreas and feces were similar to that in WT mice, indicating the absence of systemic dyslipidemia and ectopic lipid deposition in primary metabolic organs under TRIF deficiency. In summary, TRIF was involved in the regulation of adipogenesis and adipocyte enlargement, contributing to the progression of AT remodeling. This study advanced our understanding of the role of TRIF in the AT metabolic regulation.