Ultrasound-induced adiponectin release in subcutaneous adipose tissue: implications for obesity treatment.

BACKGROUND: Obesity affects more than one billion individuals worldwide and increases the risk of type 2 diabetes, cardiovascular disease, hypertension, and several cancers. In this study, we investigated a nonpharmacological, nonsurgical alternative obesity treatment via the use of low-intensity ultrasound-based therapy. We evaluated the safety and efficacy of varying frequency and intensity parameters on inducing the release of the adipokine adiponectin, which is linked to many metabolic and anti-inflammatory processes. METHODS: Subcutaneous adipose tissue (SAT) explants from healthy 7-8-week-old Sprague-Dawley rats were submerged in 5 mM glucose Krebs-Ringer buffer and exposed to continuous-wave ultrasound (400, 600, or 800 kHz; 0.3, 0.5, or 1.0 W/cm2; n = 6-9 per condition/sex), or were sham treated. Extracellular adiponectin levels were measured by ELISA at baseline, 5 min, and 30 min post-treatment. Histological integrity was assessed using H&E staining. RESULTS: The highest net adiponectin gain (Δ = t30min - t0min) occurred at 600 kHz and 0.3 W/cm2, with a 162.4 × increase relative to sham (1674.0 ± 661.1 ng/mL; Tukey-adjusted p < 0.0001) at 30 min. At 400 kHz, 0.3 W/cm2 increased secretion 10.7 × versus sham (110.3 ± 19.0 ng/mL; p < 0.001). At 800 kHz, a comparable effect required 1.0 W/cm2 (200.6 ± 69.0 ng/mL; p < 0.0001), producing a 19.5 × increase. Female-derived tissue exhibited greater responsiveness than male-derived tissue at multiple intensities of 400 kHz and 800 kHz (p < 0.05). Histology confirmed preserved adipocyte morphology and absence of necrosis or inflammatory infiltration across conditions. CONCLUSION: Within the tested range, these findings suggest that low-intensity ultrasound, particularly at 600 kHz and moderate intensities (0.3 and 0.5 W/cm2), enhanced adiponectin secretion without compromising tissue integrity. These findings support further investigation of ultrasound as a potential noninvasive strategy for modulating adipose endocrine function.