Interferon beta overexpression attenuates adipose tissue inflammation and high-fat diet-induced obesity and maintains glucose homeostasis

Abstract

The worldwide prevalence of obesity is increasing, raising health concerns regarding obesity-related complications. Chronic inflammation has been characterized as a major contributor to the development of obesity and obesity-associated metabolic disorders. The purpose of the current study is to assess whether overexpression of interferon beta (IFNβ1), an immune-modulating cytokine, will attenuate high fat diet-induced adipose inflammation and protect animals against obesity development. Using hydrodynamic gene transfer to elevate and sustain blood concentration of IFNβ1 in mice fed a high fat diet, we showed that overexpression of Ifnβ1 gene markedly suppressed immune cell infiltration into adipose tissue, and attenuated production of pro-inflammatory cytokines. Systemically, IFNβ1 blocked adipose tissue expansion and body weight gain, independent of food intake. Possible browning of white adipose tissue might also contribute to blockade of weight gain. More importantly, IFNβ1 improved insulin sensitivity and glucose homeostasis. These results suggest that targeting inflammation represents a practical strategy to block the development of obesity and its related pathologies. In addition, IFNβ1-based therapies have promising potential for clinical applications for the prevention and treatment of various inflammation-driven pathologies.

The intestinal microbial metabolite desaminotyrosine is an anti‐inflammatory molecule that modulates local and systemic immune homeostasis

“…Alsaggar et al showed that IFNβ1 blocked adipose tissue expansion and body weight gain, independent of food intake. 34 Similarly, Wieser et al showed type-I IFN responses in adipose tissue protects against metabolic dysfunction. 35 However, the role of type-I IFN pathway in obesity remains obscure, since conflicting results were reported in the literature.…”

A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

“…Alsaggar et al [98] found that IFN-b overexpression suppresses adipose inflammation induced by a high-fat diet, inhibits the infiltration of immune cells into adipose tissues and reduces proinflammatory cytokine production in mice on a high-fat diet. Indeed, viral infections and lipid metabolism disorder were the major events in this group.…”

“…Indeed, viral infections and lipid metabolism disorder were the major events in this group. Alsaggar et al [98] found that IFN-b overexpression suppresses adipose inflammation induced by a high-fat diet, inhibits the infiltration of immune cells into adipose tissues and reduces proinflammatory cytokine production in mice on a high-fat diet. Croze et al [99] described that IFN-b regulates metabolic processes which control the balance of fatty acids and derived biomolecules.…”

South Asian men have lower expression of IFN signalling genes in white adipose tissue and skeletal muscle compared with white men

“…Interestingly, adipose tissue-specific knockout of Ifna1 or Ifnb1 in mice reduces high-fat-diet-induced weight gain, insulin resistance and glucose intolerance [4]. IFNβ1 induces cellular glucose uptake via the phosphoinositide 3-kinase (PI3K)/ Akt pathway [5] and overexpression of Ifnb1 suppresses adipose tissue inflammation and protects against diet-induced obesity and glucose intolerance [6]. Together, this suggests that impaired IFN signalling in South Asian people may, at least partly, contribute to their predisposition for development of obesity as well as type 2 diabetes.…”