Abstract
Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an emerging non-invasive technology that modulates inflammation. Here, we reasoned that focused ultrasound stimulation of the liver may alleviate obesity-related inflammation and other comorbidities. After 8 weeks on a high-fat high-carbohydrate “Western” diet, C57BL/6J mice were subjected to either sham stimulation or focused ultrasound stimulation at the porta hepatis. Daily liver-focused ultrasound stimulation for 8 weeks significantly decreased body weight, circulating lipids and mitigated dysregulation of adipokines. In addition, liver-focused ultrasound stimulation significantly reduced hepatic cytokine levels and leukocyte infiltration. Our findings demonstrate the efficacy of hepatic focused ultrasound for alleviating obesity and obesity-associated complications in mice. These findings suggest a previously unrecognized potential of hepatic focused ultrasound as a possible novel noninvasive approach in the context of obesity.
Highlights
Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality
Kcal from fat) high-carbohydrate (55% fructose and 45% glucose supplement in water) “Western diet” or lowfat (10% kcal from fat, calorie matched to the high-fat diet) low carbohydrate “control diet” for 8 weeks prior to stimulation (Fig. 1B)
Beginning at week 9, mice on both diets were randomized into two subgroups that received either daily sham stimulation or Peripheral focused ultrasound stimulation (pFUS) targeted to the porta hepatis for the remainder of the study, until week 16 (Fig. 1A,B)
Summary
A growing health concern, is associated with an increased risk of morbidity and mortality. Obesity is associated with increased mortality and a number of comorbidities, such as insulin resistance, metabolic syndrome, cardiovascular disease, high cholesterol, type 2 diabetes mellitus, coronary artery disease, and nonalcoholic fatty liver disease [2,3,4]. Together, these complications result in a net global economic impact of $2.0 trillion 5. Clinical studies using implanted nerve stimulators indicate VNS can induce weight reduction in obese patients 19 Together, these studies suggest that peripheral inflammation and peripheral nervous system are involved in the metabolic dysfunctions associated with obesity
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