Abstract
The vagus nerve (VN) and spleen represent a complex interface between neural and immunological functions, affecting both energy metabolism and white adipose tissue (WAT) content. Here, we evaluated whether vagal and splenic axis participates in WAT mass regulation in obese and non-obese male Wistar rats. High doses of monosodium glutamate (M; 4 g/Kg) were administered during the neonatal period to induce hypothalamic lesion and obesity (M-Obese rats). Non-obese or Control (CTL) rats received equimolar saline. At 60 days of life, M-Obese and CTL rats were randomly distributed into experimental subgroups according to the following surgical procedures: sham, subdiaphragmatic vagotomy (SV), splenectomy (SPL), and SV + SPL (n = 11 rats/group). At 150 days of life and after 12 h of fasting, rats were euthanized, blood was collected, and the plasma levels of glucose, triglycerides, cholesterol, insulin, and interleukin 10 (IL10) were analyzed. The visceral and subcutaneous WAT depots were excised, weighed, and histologically evaluated for number and size of adipocytes as well as IL10 protein expression. M-Obese rats showed higher adiposity, hyperinsulinemia, hypertriglyceridemia, and insulin resistance when compared with CTL groups (p < 0.05). In CTL and M-Obese rats, SV reduced body weight gain and triglycerides levels, diminishing adipocyte size without changes in IL10 expression in WAT (p< 0.05). The SV procedure resulted in high IL10 plasma levels in CTL rats, but not in the M-Obese group. The splenectomy prevented the SV anti-adiposity effects, as well as blocked the elevation of IL10 levels in plasma of CTL rats. In contrast, neither SV nor SPL surgeries modified the plasma levels of IL10 and IL10 protein expression in WAT from M-Obese rats. In conclusion, vagotomy promotes body weight and adiposity reduction, elevating IL10 plasma levels in non-obese animals, in a spleen-dependent manner. Under hypothalamic obesity conditions, VN ablation also reduces body weight gain and adiposity, improving insulin sensitivity without changes in IL10 protein expression in WAT or IL10 plasma levels, in a spleen-independent manner. Our findings indicate that the vagal-spleen axis influence the WAT mass in a health state, while this mechanism seems to be disturbed in hypothalamic obese animals.
Highlights
White adipose tissue (WAT) exerts a central role in energy homeostasis, a function related to the endocrine activities of adipocytes (Ghaben and Scherer, 2019)
It is widely accepted that Autonomic nervous system (ANS) and immunological functions are differently modulated in obese and non-obese states and that changes in neuro-immune axis explain many comorbidities related to WAT mass expansion (Balbo et al, 2016; Mauer et al, 2016; Gotoh et al, 2017)
The impact of vagus nerve (VN) ablation in adiposity in non-obese animals may be dependent on the presence of spleen and changes in interleukin 10 (IL10) plasma levels
Summary
White adipose tissue (WAT) exerts a central role in energy homeostasis, a function related to the endocrine activities of adipocytes (Ghaben and Scherer, 2019). Adipocytes present a narrow association between metabolism (lipogenesis and lipolysis), cell size (larger and small cells), and adipokine secretion (pro or anti-inflammatory substances) (Gustafson and Smith, 2015). In obesity conditions, the pronounced WAT expansion is primarily characterized by increased lipogenesis, adipocyte hypertrophy, and increases in pro-inflammatory proteins, such as tumor necrosis factor-alpha (TNFα) and interleukin 1 beta (IL1β), with simultaneous reduction in antiinflammatory substances, such as interleukin 10 (IL10) and adiponectin (Van Meijel et al, 2019). The origin of these processes is unknown. In this sense, the interplay of neuronal and immunological aspects seems to have an important impact in metabolic diseases, including those associated with WAT expansion (Seoane-Collazo et al, 2015). Two central arms in the immune and metabolic interface are the bi-directional influence of the vagus nerve (VN) and spleen on WAT function (Martin et al, 2015; Pavlov and Tracey, 2017; Ai et al, 2018)
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