Cover Story Current Issue

Consuming small amounts of palatable food, i.e., snacking, at various times of the day is a highly prevalent behavior in most modern societies. Chronic rest-phase food intake – especially of high-caloric items – promotes obesity and disrupts endogenous circadian rhythms. Notably, humans and mice are more prone to hedonically driven eating behavior, the overconsumption of palatable food, during the late active/early inactive phase, i.e., the morning in mice, the evening in humans. While the effects of calorie-dense food items in promoting body weight gain are well documented, the metabolic impact of snack timing is far less understood.

Kimberly Begemann, Isabel Heyde, Pia Witt, Julica Inderhees, ... Henrik Oster

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Current Issue

Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis

Hélène Dehondt, Arianna Marino, Laura Butruille, Denis A. Mogilenko, ... Bart Staels

Objective

Obesity is associated with metabolic dysfunction of white adipose tissue (WAT). Activated adipocytes secrete pro-inflammatory cytokines resulting in the recruitment of pro-inflammatory macrophages, which contribute to WAT insulin resistance. The bile acid (BA)-activated nuclear Farnesoid X Receptor (FXR) controls systemic glucose and lipid metabolism. Here, we studied the role of FXR in adipose tissue function.

Methods

We first investigated the immune phenotype of epididymal WAT (eWAT) from high fat diet (HFD)-fed whole-body FXR-deficient (FXR−/−) mice by flow cytometry and gene expression analysis. We then generated adipocyte-specific FXR-deficient (Ad-FXR−/−) mice and analyzed systemic and eWAT metabolism and immune phenotype upon HFD feeding. Transcriptomic analysis was done on mature eWAT adipocytes from HFD-fed Ad-FXR−/− mice.

Results

eWAT from HFD-fed whole-body FXR−/− and Ad-FXR−/− mice displayed decreased pro-inflammatory macrophage infiltration and inflammation. Ad-FXR−/− mice showed lower blood glucose concentrations, improved systemic glucose tolerance and WAT insulin sensitivity and oxidative stress. Transcriptomic analysis identified Gsta4, a modulator of oxidative stress in WAT, as the most upregulated gene in Ad-FXR−/−mouse adipocytes. Finally, chromatin immunoprecipitation analysis showed that FXR binds the Gsta4 gene promoter.

Conclusions

These results indicate a role for the adipocyte FXR-GSTA4 axis in controlling HFD-induced inflammation and systemic glucose homeostasis.

 

Articles in Press

Adipocyte-specific FXR-deficiency protects adipose tissue from oxidative stress and insulin resistance and improves glucose homeostasis

Hélène Dehondt, Arianna Marino, Laura Butruille, Denis A. Mogilenko, ... Bart Staels

Objective

Obesity is associated with metabolic dysfunction of white adipose tissue (WAT). Activated adipocytes secrete pro-inflammatory cytokines resulting in the recruitment of pro-inflammatory macrophages, which contribute to WAT insulin resistance. The bile acid (BA)-activated nuclear Farnesoid X Receptor (FXR) controls systemic glucose and lipid metabolism. Here, we studied the role of FXR in adipose tissue function.

Methods

We first investigated the immune phenotype of epididymal WAT (eWAT) from high fat diet (HFD)-fed whole-body FXR-deficient (FXR−/−) mice by flow cytometry and gene expression analysis. We then generated adipocyte-specific FXR-deficient (Ad-FXR−/−) mice and analyzed systemic and eWAT metabolism and immune phenotype upon HFD feeding. Transcriptomic analysis was done on mature eWAT adipocytes from HFD-fed Ad-FXR−/− mice.

Results

eWAT from HFD-fed whole-body FXR−/− and Ad-FXR−/− mice displayed decreased pro-inflammatory macrophage infiltration and inflammation. Ad-FXR−/− mice showed lower blood glucose concentrations, improved systemic glucose tolerance and WAT insulin sensitivity and oxidative stress. Transcriptomic analysis identified Gsta4, a modulator of oxidative stress in WAT, as the most upregulated gene in Ad-FXR−/−mouse adipocytes. Finally, chromatin immunoprecipitation analysis showed that FXR binds the Gsta4 gene promoter.

Conclusions

These results indicate a role for the adipocyte FXR-GSTA4 axis in controlling HFD-induced inflammation and systemic glucose homeostasis.

 

2021 impact factor: 8.568

You are what you eat

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