Effect of the cholinergic pathway in cellular and metabolic changes in the adipose tissue

Author(s)

Luísa Menezes Silva

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2021-02-01

Examining board members

Denise Morais da Fonseca; José Carlos Farias Alves Filho; Alessandro dos Santos Farias; José Donato Júnior

• Advisor: Denise Morais da Fonseca

Abstract

Understand the mechanisms that support metabolic and immunological homeostasis in the different adipose tissue compartments is essential since these tissues actively contribute to the origin of metabolic disorders. Cholinergic inflammation control is one of the most studied neuroimmune mechanisms today. However, little is known about the influence of acetylcholine on the immune and metabolic homeostasis of adipose tissue. Our goal is to understand the communication between the nervous and immune systems in the context of cellular and metabolic changes in adipose tissue. For this, we used VACht knockdown (KD) transgenic mice, pharmacologically treated or vagotomized (VgX) to characterize immune cells in the adipose tissue compartments in acetylcholine deficiency (ACh). Significant enrichment was found in the infiltrate of cells and cytokines related to the Th2 response profile in animals with reduced ACh signaling. This was observed mainly in the mesenteric adipose tissue (mesWAT), but not in the subcutaneous adipose tissue, mesenteric lymph node or spleen of these animals. Then, in order to understand the metabolic impact on adipose tissue driven by the cholinergic pathway, we treated mice with a high-fat diet (HFD) to induce obesity. HFD-treated mice with cholinergic pathway showed better metabolic performance compared to controls, such as reduced weight gain, better insulin response and less fat accumulation. In addition, the cell populations present in the mesenteric adipose tissue of these obese animals produce more cytokines of the Th2 profile compared to the control group on the same diet. Finally, we analyze the role of cholinergic innervation and production of acetylcholine by cells from different tissues. We have seen that the density of cholinergic fibers and cells that produce acetylcholine is different between adipose tissue deposits, being higher in visceral tissues. In particular, mesWAT innate lymphoid cells (ILCs) have a high density of the acetylcholine-producing enzyme. Thus, our data suggest that the cholinergic system can control the immune tone of adipose tissue compartments, mainly visceral, and may be involved in the development of metabolic disorders. (AU)

• FAPESP's process: 18/15981-0 - Effect of anti-inflammatory cholinergic pathway in the metabolic changes following high fat diets
• Grantee: Luísa Menezes Silva
• Support Opportunities: Scholarships in Brazil - Master