Low-intensity Pulsed Ultrasound Ameliorates Obesity-induced Hepatic Lipid Metabolic Disorders

To investigate the therapeutic potential of low-intensity pulsed ultrasound (LIPUS) in ameliorating obesity-induced hepatic steatosis and exploring its underlying mechanisms.

Thirty male C57BL/6J mice were divided into normal diet (ND), high-fat diet (HFD), and HFD with LIPUS treated (HFD + LIPUS) groups. The ND group was fed standard diet throughout the 12-wk experimental period. The HFD and HFD + LIPUS groups received high-fat diet for the first 8 wk and were then switched to standard diet for the remaining 4 wk. During the final 4 wk, the HFD + LIPUS group received daily 20-min LIPUS irradiation targeting the hepatic region.

HFD-induced metabolic abnormalities including obesity, dyslipidemia, hepatic dysfunction and steatosis were significantly improved by LIPUS. Molecular analysis showed LIPUS coordinately regulated lipid metabolic enzymes by upregulating ATGL/HSL and downregulating ACLY/FASN in both liver and epididymal white adipose tissue (eWAT). Mechanistically, LIPUS activated hepatic Piezo1-PI3K/AKT signaling while suppressing mTOR phosphorylation. Simultaneously, LIPUS stimulated hepatic FGF21 secretion and activated the FGFR1/KLB-PPAR-γ-PGC-1α-UCP-1 pathway in eWAT.

LIPUS ameliorates hepatic steatosis by Piezo1-mediated hepatic lipid metabolic regulation and FGF21-driven adipose tissue browning, providing a novel non-invasive therapeutic strategy for obesity-related metabolic disorders.