Neuroendocrine Regulation of Energy Metabolism Involving Different Types of Adipose Tissues

Abstract

Despite tremendous research efforts to identify regulatory factors that control energy metabolism, the prevalence of obesity has been continuously rising, with nearly 40% of US adults being obese. Interactions between secretory factors from adipose tissues and the nervous system innervating adipose tissues play key roles in maintaining energy metabolism and promoting survival in response to metabolic challenges. It is currently accepted that there are three types of adipose tissues, white (WAT), brown (BAT), and beige (BeAT), all of which play essential roles in maintaining energy homeostasis. WAT mainly stores energy under positive energy balance, while it releases fuels under negative energy balance. Thermogenic BAT and BeAT dissipate energy as heat under cold exposure to maintain body temperature. Adipose tissues require neural and endocrine communication with the brain. A number of WAT adipokines and BAT batokines interact with the neural circuits extending from the brain to cooperatively regulate whole-body lipid metabolism and energy homeostasis. We review neuroanatomical, histological, genetic, and pharmacological studies in neuroendocrine regulation of adipose function, including lipid storage and mobilization of WAT, non-shivering thermogenesis of BAT, and browning of BeAT. Recent whole-tissue imaging and transcriptome analysis of differential gene expression in WAT and BAT yield promising findings to better understand the interaction between secretory factors and neural circuits, which represents a novel opportunity to tackle obesity.

Keywords: RNA sequencing; adipokines; batokines; beige adipose tissue; brown adipose tissue; denervation; fatty acid oxidation; high-fat diet; innervation; lipolysis; sympathetic nervous system; thermogenesis; white adipose tissue.

Figure 1

Neuroendocrine regulation of lipid metabolism at different types of adipose tissues. A two-way communication exists between the brain and white, brown and beige adipose tissues (WAT, BAT and BeAT, respectively) involving neural signals consisting of afferent sensory nerves (green arrows) and efferent sympathetic nerves (brown arrows), and endocrine signals (red arrows) consisting of WAT adipokines and BAT batokines. Environmental stimuli (i.e., diet, temperature, exercise, fasting) that change energy stores modulate sympathetic activity to regulate lipolysis, lipogenesis, and adipokine secretion at WAT; thermogenesis, fatty acid oxidation, and batokine secretion at BAT; and induction of BeAT and browning. A number of WAT adipokines (such as leptin and adiponectin) and BAT batokines (such as fibroblast growth factor 21 [FGF21] and interleukin 6 [IL-6]) interact with neural circuits to cooperatively regulate whole-body energy metabolism.

Figure 2

Schematic overview of location of different types of white and brown adipose tissues. Schematic diagrams indicating locations of different types of commonly studied WAT and BAT commonly studied in male and female rodent models, including visceral RWAT, MWAT, and GWAT, as well as subcutaneous IWAT and interscapular BAT.

Figure 3

Schematic overview of function of sympathetic innervation of white and brown adipose tissues in the regulation of lipid metabolism. Schematic diagram indicating lipolysis and thermogenesis in white and brown adipocytes respectively regulated by sympathetic innervation. In white adipocytes, sympathetic innervation regulates a cascade of lipolysis to convert stored triglycerides (TG) to free fatty acids (FFA) and glycerol that can be used as fuels of other tissues. In brown adipocytes, sympathetic innervation regulates non-shivering thermogenesis. FFAs are transferred into mitochondria, primarily by carnitine palmitoyltransferase 1 (CPT1), and serve as fuel for β-oxidation. UCP1 is activated to disassociate respiratory chain from ATP production, and ultimately dissipates energy as heat.