Effects of knee loading on obesity‐related nonalcoholic fatty liver disease in an ovariectomized mouse model with high fat diet

Abstract

Aim Hormonal and nutritional disorders are the main causes of obesity and nonalcoholic fatty liver disease, especially in the elderly and postmenopausal women. Although physical activity may alleviate these disorders, the elderly may often have difficulty in conducting physical exercise. The purpose of this study was to investigate the therapeutic effect of knee loading, a new form of physical stimulation, on the symptom of obesity and fatty liver. Methods Using ovariectomized mice with high fat diet, we evaluated the effect of knee loading that applies gentle cyclic loads to the knee. Female C57BL/6 mice were divided into five groups: control (SCD), high fat diet (HF), HF with loading (HF+L), HF with ovariectomy (HF+OVX), and HF+OVX with loading (HF+OVX+L). Except for SCD, mice underwent sham operation or ovariectomy and maintained on high fat diet. After 6 weeks, the mice in HF+L and HF+OVX+L were treated with 6‐week knee loading. Results Compared to the obesity groups (HF and HF+OVX), knee loading significantly decreased a gain in body weight, liver weight, and white adipose tissue (all P<0.01). It also reduced the lipid level in the serum (P<0.01) and histological severity of hepatic steatosis (P<0.01). Furthermore, knee loading downregulated biomarkers related to the endoplasmic reticulum stress (GRP78, p‐eIF2α and ATF4) and altered biomarkers in autophagy (LC3 and p62). Conclusions Knee loading suppressed obesity‐associated metabolic alterations and hepatic steatosis, the effect with knee loading might be associated with suppression of the ER stress and promotion of autophagy.