A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue

Abstract

Background/Objectives:Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity.Methods:In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR.Results & Conclusions:Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain.

Changes in systemic and subcutaneous adipose tissue inflammation and oxidative stress in response to exercise training in obese black African women

“…Additionally, recent evidence showed that inflammation in the adipocyte microenvironment is required for extracellular matrix remodelling and angiogenesis (Cristancho & Lazar, 2011;Asterholm et al 2014). Fat mass reduction driven by an overall reduction of stored triglycerides consecutive to lipolysis requires extensive remodelling of the tissue (Pasarica et al 2009;Fischer et al 2018). Exercise training increases basal and/or stimulated adipocyte lipolysis (Després et al 1984;Teixeira et al 2016).…”

Heterogeneity of adipose tissue in development and metabolic function

“…In contrast, reaching the lipid storage capacity of VAT promotes ectopic lipid accumulation outside of adipose tissues, promoting insulin resistance and glucose intolerance. Moreover, we and others have reported that even after weight loss, a history of obesity leaves a specific inflammatory fingerprint within pgWAT, together with persistent hypertrophy (Fischer et al, 2017), macrophage infiltration and secretion of pro-inflammatory cytokines (Schmitz et al, 2016;Zamarron et al, 2017), whereas there is little difference between the psWAT of obese mice and that of lean mice. This suggests that factors intrinsic to adipose tissue regulate the capacity to store lipids and to maintain adipocyte function.…”

Amelioration of Metabolic Syndrome in High Fat Fed Mice by Hydro-Ethanolic Fraction of M. longifolia (J. Koenig)

“…The size of adipocytes were also decreased w.r.t to diseased group (obesity control). [28][29] None of the murines showed gross and significant microscopic renal or pancreatic abnormality.…”