Roles of the vestibular system in obesity and impaired glucose metabolism in high-fat diet-fed mice

Abstract

The vestibular system controls balance, posture, blood pressure, and gaze. However, the roles of the vestibular system in energy and glucose metabolism remain unknown. We herein examined the roles of the vestibular system in obesity and impaired glucose metabolism using mice with vestibular lesions (VL) fed a high-sucrose/high-fat diet (HSHFD). VL was induced by surgery or arsenic. VL significantly suppressed body fat enhanced by HSHFD in mice. Glucose intolerance was improved by VL in mice fed HSHFD. VL blunted the levels of adipogenic factors and pro-inflammatory adipokines elevated by HSHFD in the epididymal white adipose tissue of mice. A β-blocker antagonized body fat and glucose intolerance enhanced by HSHFD in mice. The results of an RNA sequencing analysis showed that HSHFD induced alterations in genes, such as insulin-like growth factor-2 and glial fibrillary acidic protein, in the vestibular nuclei of mice through the vestibular system. In conclusion, we herein demonstrated that the dysregulation of the vestibular system influences an obese state and impaired glucose metabolism induced by HSHFD in mice. The vestibular system may contribute to the regulation of set points under excess energy conditions. OPEN ACCESS Citation: Kawao N, Takafuji Y, Ishida M, Okumoto K, Morita H, Muratani M, et al. (2020) Roles of the vestibular system in obesity and impaired glucose metabolism in high-fat diet-fed mice. PLoS ONE 15 (2): e0228685. https://doi.org/10.sympathetic nervous system in rodents [4,5]. Luxa et al. reported that labyrinthectomy increased myofiber remodeling in the soleus muscle of mice [6]. We recently revealed that gravity changes affect muscle and bone through the vestibular system in mice [7,8]. Collectively, these findings suggest that the vestibular system regulates the musculoskeletal system partly through the sympathetic nervous system. Dysfunctions in the vestibular system clinically cause dizziness, vertigo, and unsteadiness [9]. Long-term space flight impairs the vestibular system in astronauts who experience orthostatic intolerance and unsteadiness [3]. However, the roles of the vestibular system in metabolic homeostasis have not yet been elucidated in detail.Excess energy is stored in white adipose tissue (WAT) as lipids and causes obesity, a risk factor for diabetes [10]. Adipocytes differentiate from mesenchymal stem cells, and the activation of adipogenic differentiation is followed by enhanced levels of peroxisome proliferatoractivated receptor γ (PPARγ), aP2, long chain acyl-CoA synthetase (ACSL) 1, and lipoprotein lipase (LPL). In obesity, WAT releases pro-inflammatory adipokines, such as tumor necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1, and monocyte chemoattractant protein (MCP)-1, which impair glucose metabolism due to the induction of low-grade systemic inflammation [10]. Adiponectin and leptin released from adipose tissue exert pleiotropic effects in glucose metabolism [10]. Circulating adiponectin and leptin produced from WAT are negatively and positively r...

Effectiveness of 12 weeks of electrical vestibular nerve stimulation in the management of obesity: A pilot study

“…17 Vestibular stimulation was 18 Animal studies have demonstrated a decrease in body weight followed by caloric vestibular stimulation. 6,7 Human studies also reported regulation of lipid profile followed by vestibular stimulation. 19,20 The present study results support earlier studies as there is a decrease in the body weight of the participants.…”

“…6 Vestibular dysregulation was reported to influence obesity and vestibular stimulation was reported to alter the set point of fat. 7,8 Although there are multiple methods available to stimulate the vestibular system, optimal stimulation is required to avail maximum beneficial effects. Electrical vestibular stimulation is a simple and non-invasive method and can control the strength of the stimulation offered.…”

“…It was hypothesized that electrical vestibular nerve stimulation (VeNs) was an effective therapy in the management of obesity. 7 Hence, the present pilot study was undertaken to observe the efficacy of 12-week electrical VeNs in the management of obesity.…”

Beneficial Effects of Vestibular Exercise Along with Yoga on Diabetes Mellitus: A Review

“…Vestibular stimulation plays an important role in food intake [40]. Obesity is observed in DM due to insulin resistance.…”

Vestibular Nerve Stimulation as a Potential New Therapeutic Modality for Type 2 Diabetes Mellitus

“…We pointed out that that the vestibular system appears to play a key (though much underrecognized) role in metabolic homeostasis. This is reflected neuroanatomically by vestibular projections to multiple brainstem and hypothalamic nuclei involved in the central control of metabolism, including: the central melanocortin system (CMS) that is involved in appetite regulation and fixing a set-point for body fat; major parasympathetic sites; and centers that regulate brown adipose tissue (BAT) [1][2][3].…”