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Ultrasound-Induced Adiponectin Release in Subcutaneous Adipose Tissue: Implications for Obesity Treatment

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Obesity, a growing global health crisis, affects over 2 billion individuals worldwide, is strongly associated with an increased risk of type 2 diabetes, cardiovascular disease, hypertension, and multiple cancers. In 2019 alone, obesity-related noncommunicable diseases accounted for an estimated 5 million deaths globally. Current pharmacological interventions—such as GLP-1 receptor agonists and orlistat—are effective but carry adverse effects, while bariatric surgery, although more effective, poses surgical risks. but carries greater risks due to surgical complications. These limitations highlight the need for safer, non-invasive therapeutic alternatives. This study investigated the safety and efficacy of ultrasound in modulating adiponectin secretion from subcutaneous adipose tissue (SAT). SAT samples from 7-8-week-old Sprague-Dawley rats were submerged in 5 mM glucose Krebs-Ringer buffer and exposed at 400, 600, and 800 kHz, under intensities of 0.3, 0.5, and 1.0 W/cm² (n = 6). Extracellular adiponectin levels were quantified using a 4-parameter logistic (4PL) ELISA at baseline, 5 min, and 30 min post-treatment. The highest net adiponectin gain (Δ = t₃₀ - t₀) was observed at 600 kHz and 0.3 W/cm² (Δ = 674.03 ng/mL, p < 0.001), significantly greater than sham (Δ = 21.45 ng/mL). At 800 kHz, adiponectin release was intensity-dependent, with 1.0 W/cm² yielding the highest gain (Δ = 200.6 ng/mL). Tissue viability, assessed via Trypan Blue staining at 400 kHz, showed highest viability at 0.5 W/cm² (76% live cells), while 1.0 W/cm² resulted in reduced viability (64%) and the highest cell death (37%). Histological analysis revealed intact adipocyte morphology across most conditions, with mild adipocyte remodeling at higher intensities, particularly at 800 kHz and 1.0 W/cm². Collectively, these findings suggest that ultrasound, particularly at 600 kHz and moderate intensities (0.3 and 0.5 W/cm²), effectively stimulates adiponectin secretion without compromising tissue integrity. This supports ultrasound as a promising non-invasive candidate for future obesity interventions.

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