Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease.

Rachel B Wilson,Yun Jin Chen,Kelly-Ann Leonard,René L Jacobs,Krisha Patel,Brian G Sutherland,Rennian Wang,John P Kennelly,Richard Zhang,Cynthia G Sawyez,Kia M Peters,Nica M Borradaile

doi:10.3390/ijms21239156

Rachel B Wilson, Yun Jin Chen + Show 10 more

Open Access

https://doi.org/10.3390/ijms21239156

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Abstract

Prolonged, isocaloric, time-restricted feeding (TRF) protocols can promote weight loss, improve metabolic dysregulation, and mitigate non-alcoholic fatty liver disease (NAFLD). In addition, 3-day, severe caloric restriction can improve liver metabolism and glucose homeostasis prior to significant weight loss. Thus, we hypothesized that short-term, isocaloric TRF would improve NAFLD and characteristics of metabolic syndrome in diet-induced obese male mice. After 26 weeks of ad libitum access to western diet, mice either continued feeding ad libitum or were provided with access to the same quantity of western diet for 8 h daily, over the course of two weeks. Remarkably, this short-term TRF protocol modestly decreased liver tissue inflammation in the absence of changes in body weight or epidydimal fat mass. There were no changes in hepatic lipid accumulation or other characteristics of NAFLD. We observed no changes in liver lipid metabolism-related gene expression, despite increased plasma free fatty acids and decreased plasma triglycerides in the TRF group. However, liver Grp78 and Txnip expression were decreased with TRF suggesting hepatic endoplasmic reticulum (ER) stress and activation of inflammatory pathways may have been diminished. We conclude that two-week, isocaloric TRF can potentially decrease liver inflammation, without significant weight loss or reductions in hepatic steatosis, in obese mice with NAFLD.

Highlights

Treatment strategies for non-alcoholic fatty liver disease (NAFLD) encompass behavioural, pharmacological, and surgical approaches primarily focused on improving blood glucose, triglycerides, and cholesterol—the metabolic parameters associated with this disease [1,2]
We hypothesized that short-term, isocaloric time-restricted feeding (TRF) would diminish NAFLD severity and improve metabolic parameters associated with liver function
Liver steatosis is the first step in the pathogenesis of NAFLD/non-alcoholic steatohepatitis (NASH), as it can lead to sustained hepatic inflammation through hepatocyte insulin resistance, endoplasmic reticulum (ER) stress, and progressive cellular dysfunction [3,15]

Summary

Introduction

Treatment strategies for non-alcoholic fatty liver disease (NAFLD) encompass behavioural, pharmacological, and surgical approaches primarily focused on improving blood glucose, triglycerides, and cholesterol—the metabolic parameters associated with this disease [1,2]. Behavioural modifications aimed at weight loss are effective in improving many components of metabolic syndrome [3], thresholds of 5–10% and >10% weight loss are needed to reduce steatosis and improve non-alcoholic steatohepatitis (NASH), respectively [3]. To this end, bariatric surgery has become an increasingly common treatment for obesity and its complications. In the absence of bariatric surgery, achieving sufficient weight loss can be challenging for individuals with obesity-associated conditions that may limit physical activity In such cases, alternative dietary protocols could be especially useful. Time-restricted feeding (TRF) protocols, including intermittent fasting, in which food consumption is restricted to specific times in the day, have garnered intense public interest as potential treatments for obesity and obesity-related diseases [4]

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