Neural innervation of white adipose tissue and the control of lipolysis

Abstract

White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS) and its activation is necessary for lipolysis. WAT parasympathetic innervation is not supported. Fully-executed SNS-norepinephrine (NE)-mediated WAT lipolysis is dependent on β-adrenoceptor stimulation ultimately hinging on hormone sensitive lipase and perilipin A phosphorylation. WAT sympathetic drive is appropriately measured electrophysiologically and neurochemically (NE turnover) in non-human animals and this drive is fat pad-specific preventing generalizations among WAT depots and non-WAT organs. Leptin-triggered SNS-mediated lipolysis is weakly supported, whereas insulin or adenosine inhibition of SNS/NE-mediated lipolysis is strongly supported. In addition to lipolysis control, increases or decreases in WAT SNS drive/NE inhibit and stimulate white adipocyte proliferation, respectively. WAT sensory nerves are of spinal-origin and sensitive to local leptin and increases in sympathetic drive, the latter implicating lipolysis. Transsynaptic viral tract tracers revealed WAT central sympathetic and sensory circuits including SNS-sensory feedback loops that may control lipolysis.

Keywords: Denervation; Herpes simplex virus-1; Humans; Insulin; Leptin; Mice; Norepinephrine turnover; Pseudorabies virus; Rats; Siberian hamsters.

Figure 1

From: Tchkonia et al. [287] Location of major WAT depots in: A (left) – rodents (laboratory rats and mice, hamsters). Mesenteric WAT (MWAT); perigonadal [epididymal WAT (EWAT) or parametrial WAT (PWAT); perirenal WAT, retroperitoneal WAT (RWAT, not shown located in back of the peritoneal cavity); brown [interscapular brown adipose tissue (IBAT), the largest BAT depot in rodents]; subcutaneous [dorsosubcutaneous WAT (DWAT) located around front haunch; inguinal WAT (IWAT) located around rear haunch]; and B (right) – humans. Note the differences in that humans have no gonadal WAT, but rodents do, humans have omental WAT (visceral) but rodents do not but have MWAT as their only visceral WAT), rodents have subcutaneous WAT located only around the haunch area whereas subcutaneous WAT underlies the skin in most of the human body, and humans have appreciable leg WAT, but rodents do not.

Figure 2

From: A Girousse and D Langin [110] Adipocyte ‘lipolysome’ in basal and stimulated state. Lipid droplets (LDs) are surrounded by a phospholipid monolayer in which different proteins are anchored: PLIN1a (perilipin A), PLIN2 (ADRP) and Fsp27/Cidec. In the unstimulated basal state, ATGL, perilipin and ABHD5 are forming a complex at the surface of the LD. These protein interactions maintain ABHD5 inactive and as a consequence limit basal ATGL-mediated lipolysis. HSL and FABP4 are in the cytosol. In the stimulated state, HSL is phosphorylated by protein kinases (PKs); the active form of HSL migrates to the surface of the LD. PK also phosphorylate PLIN1a that undergoes structural modification and rearrangement leading to fragmentation of the LD. ABHD5 released from phosphorylated PLIN1a activates ATGL to initiate TAG hydrolysis. G0S2 can limit ATGL enzyme activity. DAGs are then transformed into MAG by active HSL. MGL ends the lipolytic process and releases glycerol and FA. FA-complexed FABP4 can interact with HSL to modulate lipolysis. ABHD5, abhydrolase domain containing; ADRP, adipose differentiation-related protein; ATGL, adipose triglyceride lipase; DAG, diacylglycerol; FA, fatty acid; FABP4, fatty acid-binding protein 4; Fsp27, fat-specific protein 27, also called Cidec; G0S2, G0/G1 switch gene 2; HSL, hormone-sensitive lipase; MAG, monoacylglycerol; MGL, monoglyceride lipase; PLIN1a, perilipin A; TAG, triacylglycerol.