Sympathoadrenal system and regulation of thermogenesis

1984 ◽  
Vol 247 (2) ◽  
pp. E181-E189 ◽  
Author(s):  
L. Landsberg ◽  
M. E. Saville ◽  
J. B. Young

The sympathetic nervous system (SNS) plays a critical role in the regulation of mammalian thermogenic responses to cold exposure and dietary intake. Catecholamine-stimulated thermogenesis is mediated by the beta-adrenergic receptor. In the rat brown adipose tissue is the major site of metabolic heat production in response to both cold (nonshivering thermogenesis) and diet (diet-induced thermogenesis). Measurements of norepinephrine turnover rate in interscapular brown adipose tissue of the rat demonstrate increased sympathetic activity in response to both cold exposure and overfeeding. In adult humans, a physiologically significant role for brown adipose tissue has not been established but cannot be excluded. It appears likely that dietary changes in SNS activity are related, at least in part, to the changes in metabolic rate that occur in association with changes in dietary intake.

1984 ◽  
Vol 247 (2) ◽  
pp. R290-R295 ◽  
Author(s):  
J. S. Fisler ◽  
T. Yoshida ◽  
G. A. Bray

Catecholamine turnover in response to fasting, cold exposure, and a high-fat diet has been measured in the Osborne-Mendel rat, which readily develops obesity when fed a high-fat diet, and the S 5B/P1 rat, which does not. We have tested the hypothesis that this difference in response to diet might be associated with altered rates of norepinephrine or epinephrine turnover. The endogenous norepinephrine concentration in interscapular brown adipose tissue was significantly greater in fasted S 5B/P1 rats than in fasted Osborne-Mendel rats. The fractional norepinephrine turnover rate in interscapular brown adipose tissue of fasted animals was also greater in the S 5B/P1 rat than in the Osborne-Mendel rat. Cold exposure increased the fractional norepinephrine turnover rate in interscapular brown adipose tissue for both strains of rats but increased the fractional norepinephrine turnover rate in the pancreas in only the Osborne-Mendel rats. The turnover of epinephrine and the adrenal concentration of this hormone were not different between the two strains. Normal and high-fat diets were fed to both strains; the Osborne-Mendel rats were pair fed the high-fat diet to prevent excess weight gain. Endogenous concentrations of norepinephrine in interscapular brown adipose tissue was increased by the high-fat diet; the increase was greater in S 5B/P1 rats. The high-fat diet resulted in increased norepinephrine turnover in interscapular brown adipose tissue of the S 5B/P1 rat but not the Osborne-Mendel rat.(ABSTRACT TRUNCATED AT 250 WORDS)


2007 ◽  
Vol 293 (2) ◽  
pp. E444-E452 ◽  
Author(s):  
Jan Nedergaard ◽  
Tore Bengtsson ◽  
Barbara Cannon

The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.


1999 ◽  
Vol 276 (6) ◽  
pp. R1569-R1578 ◽  
Author(s):  
Maryam Bamshad ◽  
C. Kay Song ◽  
Timothy J. Bartness

Brown adipose tissue (BAT) plays a critical role in cold- and diet-induced thermogenesis. Although BAT is densely innervated by the sympathetic nervous system (SNS), little is known about the central nervous system (CNS) origins of this innervation. The purpose of the present experiment was to determine the neuroanatomic chain of functionally connected neurons from the CNS to BAT. A transneuronal viral tract tracer, Bartha’s K strain of the pseudorabies virus (PRV), was injected into the interscapular BAT of Siberian hamsters. The animals were killed 4 and 6 days postinjection, and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord, brain stem, midbrain, and forebrain. The intensity of labeled neurons in the forebrain varied from heavy infections in the medial preoptic area and paraventricular hypothalamic nucleus to few infections in the ventromedial hypothalamic nucleus, with moderate infections in the suprachiasmatic and lateral hypothalamic nuclei. These results define the SNS outflow from the brain to BAT for the first time in any species.


1986 ◽  
Vol 251 (2) ◽  
pp. R240-R242 ◽  
Author(s):  
A. Niijima

The activity of sympathetic nerves innervating interscapular brown adipose tissue of the rat was recorded. Intravenous administrations of glucose (100-300 mg/kg) enhanced the nerve activity. However, mannose, fructose, or galactose (300 mg/kg) showed no effect, suggesting the response is related to diet-induced thermogenesis in the brown adipose tissue.


1987 ◽  
Vol 252 (2) ◽  
pp. R402-R408 ◽  
Author(s):  
T. Yoshida ◽  
J. S. Fisler ◽  
M. Fukushima ◽  
G. A. Bray ◽  
R. A. Schemmel

The effects of dietary fat content, lighting cycle, and feeding time on norepinephrine turnover in interscapular brown adipose tissue, heart, and pancreas, and on blood 3-hydroxybutyrate, serum glucose, insulin, and corticosterone have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to dietary obesity, have a more rapid turnover of norepinephrine in interscapular brown adipose tissue and heart and a greater increase in the concentration of norepinephrine in brown fat when eating a high-fat diet than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. Light cycle and feeding schedule are important modulators of sympathetic activity in heart and pancreas but not in brown fat. Rats of the resistant strain also have higher blood 3-hydroxybutyrate concentrations and lower insulin and corticosterone levels than do rats of the susceptible strain. A high-fat diet increases 3-hydroxybutyrate concentrations and reduces insulin levels in both strains. These studies show, in rats eating a high-fat diet, that differences in norepinephrine turnover, particularly in brown adipose tissue, may play an important role in whether dietary obesity develops and in the manifestations of resistance to this phenomenon observed in the S 5B/Pl rat.


Author(s):  
Rahel Catherina Loeliger ◽  
Claudia Irene Maushart ◽  
Gani Gashi ◽  
Jaël Rut Senn ◽  
Martina Felder ◽  
...  

Objective Human brown adipose tissue (BAT) is a thermogenic tissue activated by the sympathetic nervous system in response to cold. It contributes to energy expenditure (EE) and takes up glucose and lipids from the circulation. Studies in rodents suggest that BAT contributes to the transient rise in EE after food intake, so called diet-induced thermogenesis (DIT). We investigated the relationship between human BAT activity and DIT in response to glucose intake in 17 healthy volunteers. Methods We assessed DIT, cold induced thermogenesis (CIT) and maximum BAT activity at three separate study visits within two weeks. DIT was measured by indirect calorimetry during an oral glucose tolerance-test. CIT was assessed as the difference in EE after cold exposure of two hours duration as compared to warm conditions. Maximal activity of BAT was assessed by 18F-FDG-PET/MRI after cold exposure and concomitant pharmacological stimulation with Mirabegron. Results 17 healthy men (mean age 23.4 years, mean BMI 23.2 kg/m2) participated in the study. EE increased from 1908 (±181) kcal/24 hours to 2128 (±277) kcal/24 hours (p<0.0001, +11.5%) after mild cold exposure. An oral glucose load increased EE from 1911 (±165) kcal/24 hours to 2096 (±167) kcal/24 hours at 60 minutes (p<0.0001, +9.7%). The increase in EE in response to cold was significantly associated with BAT activity (R2=0.43, p=0.004). However, DIT was not associated with BAT activity (R2=0.015, p=0.64). Conclusion DIT after an oral glucose load was not associated with stimulated 18F-FDG uptake into BAT suggesting that DIT is independent from BAT activity in humans.


2020 ◽  
Vol 245 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Chunchun Wei ◽  
Xianhua Ma ◽  
Kai Su ◽  
Shasha Qi ◽  
Yuangang Zhu ◽  
...  

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-β is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-β inhibits BAT thermogenesis. BAT ChREBP-β mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in BAT using the Cre/LoxP approach. ChREBP-β overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-β overexpression. Mechanistically, ChREBP-β overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-β. Put together, our work points to ChREBP-β as a negative regulator of thermogenesis in brown adipocytes.


2013 ◽  
Vol 37 ◽  
pp. S60-S61
Author(s):  
Denis P. Blondin ◽  
Sébastien M. Labbé ◽  
Christophe Noll ◽  
Margaret Kunach ◽  
Éric E. Turcotte ◽  
...  

2008 ◽  
Vol 295 (2) ◽  
pp. R417-R428 ◽  
Author(s):  
C. Kay Song ◽  
Cheryl H. Vaughan ◽  
Erin Keen-Rhinehart ◽  
Ruth B. S. Harris ◽  
Denis Richard ◽  
...  

A precise understanding of neural circuits controlling lipid mobilization and thermogenesis remains to be determined. We have been studying the sympathetic nervous system (SNS) contributions to white adipose tissue (WAT) lipolysis largely in Siberian hamsters. Central melanocortins are implicated in the control of the sympathetic outflow to WAT, and, moreover, the melanocortin 4 receptors (MC4-R) appear to be principally involved. We previously found that acute third ventricular melanotan II (MTII; an MC3/4-R agonist) injections increase sympathetic drive (norepinephrine turnover) to interscapular brown adipose tissue (IBAT) and IBAT temperature. Here we tested whether MC4-R mRNA is expressed in IBAT SNS outflow neurons using in situ hybridization for the former and injections of the transneuronal viral retrograde tract tracer, pseudorabies virus (PRV) into IBAT, for the latter. Significant numbers of double-labeled cells for PRV and MC4-R mRNA were found across the neuroaxis (mean of all brain sites ∼60%), including the hypothalamic paraventricular nucleus (PVH; ∼80%). Acute parenchymal MTII microinjections into the PVH of awake, freely-moving hamsters, using doses below those able to increase IBAT temperature when injected into the third ventricle, increased IBAT temperature for as long as 4 h, as measured by temperature transponders implanted below the tissue. Collectively, these data add significant support to the view that central melanocortins are important in controlling IBAT thermogenesis via the SNS innervation of this tissue, likely through the MC4-Rs.


1999 ◽  
Vol 276 (1) ◽  
pp. R143-R151 ◽  
Author(s):  
Victoria L. King ◽  
Linda P. Dwoskin ◽  
Lisa A. Cassis

The neuronal uptake of norepinephrine (NE) in sympathetically innervated tissues is mediated by a high-affinity NE uptake transporter (NET). Rat interscapular brown adipose tissue (ISBAT) is densely innervated by the sympathetic nervous system for the control of cold- and diet-induced thermogenesis. To determine if cold exposure regulates the NET, kinetic parameters for [3H]NE uptake and [3H]nisoxetine (Nis) binding were determined in ISBAT from 7-day cold-exposed (CE) and control rats. Uptake of [3H]NE in ISBAT slices was of high affinity (1.6 μM). After 7 days of cold exposure the affinity for [3H]NE uptake was not altered; however, the uptake capacity was decreased (38%) in ISBAT slices from CE rats. Kinetic parameters for [3H]Nis binding demonstrated a single high-affinity site in ISBAT from CE and control rats with similar affinity. The density of [3H]Nis sites in ISBAT was decreased (38%) following cold exposure. A time course (2 h-7 days) for cold exposure demonstrated downregulation of [3H]Nis binding density by day 3, which remained through day 7. The affinity for [3H]Nis binding was transiently decreased at 2 h of cold exposure. Similarly, ISBAT NE content was decreased at 2 h of cold exposure. Pair feeding CE rats to food intake of controls normalized plasma NE content; however, [3H]Nis binding density in ISBAT remained decreased in pair-fed rats. These results demonstrate that the ISBAT NET is downregulated following cold exposure. Reductions in ISBAT NE content precede alterations in NET density; however, plasma NE content is not related to regulation of the NET.


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