Effects of knee loading on obesity-related non-alcoholic fatty liver disease in an ovariectomized mouse model with high-fat diet.

AIM: Hormonal and nutritional disorders are the main causes of obesity and non-alcoholic fatty liver disease, especially in the elderly and in postmenopausal women. Although physical activity might alleviate these disorders, the elderly may often have difficulty in carrying out physical exercise. The purpose of this study was to investigate the therapeutic effect of knee loading, a new form of physical stimulation, on the symptoms of obesity and fatty liver.

METHODS: Using ovariectomized mice fed a 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 were maintained on HF diet. After 6 weeks, the mice in the HF + L and HF + OVX + L groups were treated with knee loading for 6 weeks.

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 endoplasmic reticulum (ER) 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. These effects with knee loading might be associated with suppression of ER stress and promotion of autophagy.