Neural innervation of white adipose tissue and the control of lipolysis

Bartness, Timothy J.; Liu, Yang; Shrestha, Yogendra B.; Ryu, Vitaly

doi:10.1016/j.yfrne.2014.04.001

Cited by 271 publications

(284 citation statements)

References 301 publications

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“…Sympathetic activity in the adipose tissue can stimulate lipolysis directly via norepinephrine release (reviewed in Bartness et al [23]). …”

Section: Discussionmentioning

confidence: 99%

“…Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m 2 [SD 3.1]) were examined before and 23 weeks (range [19][20][21][22][23][24][25] after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery.…”

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confidence: 99%

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Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia

et al. 2016

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Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m 2 [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagonlike peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.Gastric bypass (GBP) surgery for the treatment of morbid obesity induces marked weight loss and metabolic effects.Excess BMI loss is typically ;70-80% (1), and almost instant changes occur in glucose homeostasis postsurgery, including frequent remission of diabetes up to 70% (1). After a meal, the rise in glucose and insulin is ;50% higher, reflecting the faster absorption of glucose postsurgery. Incretins are also affected; prandial gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) peak at ;2 and 10 times higher levels after surgery, respectively (2).The sustained weight loss achieved by GBP surgery, superior to that achieved by diet regimens, reflects lowered caloric intake and possibly altered secretion of gastrointestinal peptides (2). Comparing eating habits before and after the GBP surgery, patients lowered the intake with marked reductions in carbohydrate intake in the form of sweets, soda, and milk/ice cream. Fear of dumping was suggested as the main mechanism (3). Dumping can occur within 10-30 min of food intake when, in the absence of a pyloric function, it quickly enters the intestine and produces an osmotic effect. Fluid is shifted from the circulation into the intestine, resulting in a fall of blood pressure and tachycardia. In a rat model, similar food preference adaptations evolved with time, indicating that the preference shift was dependent on learning and dumping (4).In a recent study with continuous glucose monitoring (5), we observed hypoglycemic epis...

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“…Sympathetic activity in the adipose tissue can stimulate lipolysis directly via norepinephrine release (reviewed in Bartness et al [23]). …”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia

et al. 2016

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“…Finally, we also speculate that the central action of NPY (or decreased melanocortins) to increase WAT lipogenesis (64,65) is also mediated by NPY-induced decreases in SNA. The literature provides support: the melanocortin agonist MTII increases WAT SNA (65), and a decrease in WAT SNA inhibits lipolysis (66).…”

Section: Brain Viral Vector and Ctb Injectionsmentioning

confidence: 95%

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Shi¹,

Madden²,

Brooks³

2017

Journal of Clinical Investigation

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Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 6 9 jci.org Volume 127 Number 7 July 2017We next tested whether selective excitation or inhibition of ArcN NPY/AgRP neurons alters splanchnic SNA (SSNA), mean AP (MAP), or heart rate (HR) ( Figure 1). As shown in representative experiments ( Figure 1, A and B) and grouped data ( Figure 1C), in ArcN hM3Dq mice, i.p. CNO (0.3 mg/kg) promptly decreased SSNA, MAP, and HR, whereas i.p. saline had no effects. The suppression induced by CNO was sustained for at least 1 hour, and, in mice with longer recordings, up to 4 hours (data not shown). In rats, guinea pigs, and humans, CNO can have nonspecific effects due to its conversion to clozapine (17, 18). However, in WT mice receiving the Cre-dependent hM3Dq vector, neither i.p. saline nor CNO significantly altered these variables, suggesting that CNO was not exerting its effects independently of DREADD activation. A separate group of Agrp-IRES-Cre mice instead received AAV-hM4Di-mCherry in the ArcN (Figure 1, D-F). In these ArcN hM4Di mice, i.p. CNO (0.3 and 1 mg/kg) dose-dependently increased SSNA, MAP, and HR, although the responses developed both NPY-GFP and Cre in AgRP neurons. In agreement with an earlier study using a different approach (14), we found that while not all NPY-GFP neurons had visible hM3Dq-mCherry labeling, 100% of the hM3Dq-mCherry-marked neurons also expressed NPY-GFP (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI92008DS1). WT mice never expressed the Cre-dependent DREADD. In a second set of experiments, 2 or more weeks after Agrp-IRES-Cre mice received hM3Dq bilaterally in the ArcN, CNO (0.3 mg/kg) or the saline vehicle was administered i.p., and food intake was monitored for the following 4 hours. As shown previously (14), i.p. CNO, but not saline, rapidly evoked food intake in ArcN hM3Dq mice (Supplemental Figure 1). Conversely, activation of inhibitory DREADDs in ArcN hM4Di mice at the beginning of the feeding period (lights out) inhibited food intake (Supplemental Figure 1). Therefore, we anatomically and functionally confirm that this approach selectively targets ArcN NPY/AgRP neurons. The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 7 0jci.org Volume 127 Number 7 July 2017neurons were also observ...

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“…This is an important question that we are consistently asked because, as described in brief below, we were the first to demonstrate neuroanatomically the origins of the sympathetic outflow to WAT 41 and to BAT 42 using the viral transneuronal tract tracer, pseudorabies virus (PRV; for a review see Bartness et al 26,43 ). Unfortunately, because the pockets of brite/beige adipocytes are only visible microscopically and mixed among white adipocytes (for example, see Vitali et al 30 ), it is not possible to use the powerful ability of PRV to define the SNS outflow circuits from brain ultimately to these cells.…”

Section: Methodsmentioning

confidence: 99%

“…54 Similar electrophysiological responses to intra-WAT leptin injection were first reported in laboratory rat EWAT injected with this cytokine. 55,56 Just as the tips of your fingers respond to pain, temperature, vibration and position, WAT sensory innervation also may respond to several different sensory stimuli including the products of lipolysis and perhaps temperature (for review, see Bartness et al 26,43 ). Similarly, brite/beige cells in white fat depots may respond to several different stimuli including those listed above for WAT and for BAT.…”

Section: Methodsmentioning

confidence: 99%

Neural control of white, beige and brown adipocytes

Bartness

Ryu

2015

Int J Obes Supp

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Reports of brown-like adipocytes in traditionally white adipose tissue (WAT) depots occurred~30 years ago, but interest in white adipocyte 'browning' only has gained attention more recently. We integrate some of what is known about the sympathetic nervous system (SNS) innervation of WAT and brown adipose tissue (BAT) with the few studies focusing on the sympathetic innervation of the so-called 'brite' or 'beige' adipocytes that appear when WAT sympathetic drive increases (for example, cold exposure and food deprivation). Only one brain site, the dorsomedial hypothalamic nucleus (DMH), selectively browns some (inguinal WAT (IWAT) and dorsomedial subcutaneous WAT), but not all WAT depots and only when DMH neuropeptide Y gene expression is knocked down, a browning effect is mediated by WAT SNS innervation. Other studies show that WAT sympathetic fiber density is correlated with the number of brown-like adipocytes (multilocular lipid droplets, uncoupling protein-1 immunoreactivity) at both warm and cold ambient temperatures. WAT and BAT have sensory innervation, the latter important for acute BAT cold-induced temperature increases, therefore suggesting the possible importance of sensory neural feedback from brite/beige cells for heat production. Only one report shows browned WAT capable of producing heat in vivo. Collectively, increases in WAT sympathetic drive and the phenotype of these stimulated adipocytes seems critical for the production of new and/or transdifferentiation of white to brite/ beige adipocytes. Selective harnessing of WAT SNS drive to produce browning or selective browning independent of the SNS to counter increases in adiposity by increasing expenditure appears to be extremely challenging.

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Neural innervation of white adipose tissue and the control of lipolysis

Cited by 271 publications

References 301 publications

Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia

Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Neural control of white, beige and brown adipocytes

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