Nesfatin-1 Acts Centrally to Induce Sympathetic Activation of Brown Adipose Tissue and Non-Shivering Thermogenesis

2019 ◽  
Vol 51 (10) ◽  
pp. 678-685 ◽  
Author(s):  
Luka Levata ◽  
Riccardo Dore ◽  
Olaf Jöhren ◽  
Markus Schwaninger ◽  
Carla Schulz ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Body Weight Loss ◽  
Whole Body ◽  
Central Administration ◽  
Adrenergic Stimulation ◽  
Interscapular Brown Adipose Tissue ◽  
Adrenoceptor Antagonist ◽  
Brown Adipose

AbstractNesfatin-1 has originally been established as a bioactive peptide interacting with key hypothalamic nuclei and neural circuitries in control of feeding behavior, while its effect on energy expenditure has only recently been investigated. Hence, the aim of this study was to examine whether centrally acting nesfatin-1 can induce β3-adrenergic stimulation, which is a prerequisite for the activation of thermogenic genes and heat release from interscapular brown adipose tissue, key physiological features that underlie increased energy expenditure. This question was addressed in non-fasted mice stereotactically cannulated to receive nesfatin-1 intracerebroventricularly together with peripheral injection of the β3-adrenoceptor antagonist SR 59230 A, to assess whole-body energy metabolism. Using a minimally invasive thermography technique, we now demonstrate that the thermogenic effect of an anorectic nesfatin-1 dose critically depends on β3 adrenergic stimulation, as the co-administration with SR 59230 A completely abolished heat production from interscapular brown adipose tissue and rise in ocular surface temperature, thus preventing body weight loss. Moreover, through indirect calorimetry it could be shown that the anorectic concentration of nesfatin-1 augments overall caloric expenditure. Plausibly, central administration of nesfatin-1 also enhanced the expression of DIO2 and CIDEA mRNA in brown adipose tissue critically involved in the regulation of thermogenesis.

scholarly journals Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Van Schaik ◽  
C. Kettle ◽  
R. Green ◽  
W. Sievers ◽  
M. W. Hale ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Basolateral Amygdala ◽  
Free Breathing ◽  
Male Rats ◽  
Central Administration ◽  
Hypothalamic Area ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

AbstractThe role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5–10 μg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.

Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats

1986 ◽  
Vol 251 (5) ◽  
pp. E576-E583 ◽  
Author(s):  
L. H. Storlien ◽  
D. E. James ◽  
K. M. Burleigh ◽  
D. J. Chisholm ◽  
E. W. Kraegen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Brown Adipose Tissue ◽  
Whole Body ◽  
Brown Adipose ◽  
Glucose Output ◽  
Fat Feeding

High levels of dietary fat may contribute to both insulin resistance and obesity in humans but evidence is limited. The euglycemic clamp technique combined with tracer administration was used to study insulin action in vivo in liver and individual peripheral tissues after fat feeding. Basal and nutrient-stimulated metabolic rate was assessed by open-circuit respirometry. Adult male rats were pair-fed isocaloric diets high in either carbohydrate (69% of calories; HiCHO) or fat (59% of calories; HiFAT) for 24 +/- 1 days. Feeding of the HiFAT diet resulted in a greater than 50% reduction in net whole-body glucose utilization at midphysiological insulin levels (90-100 mU/l) due to both reduced glucose disposal and, to a lesser extent, failure to suppress liver glucose output. Major suppressive effects of the HiFAT diet on glucose uptake were found in oxidative skeletal muscles (29-61%) and in brown adipose tissue (BAT; 78-90%), the latter accounting for over 20% of the whole-body effect. There was no difference in basal metabolic rate but thermogenesis in response to glucose ingestion was higher in the HiCHO group. In contrast to their reduced BAT weight, the HiFAT group accumulated more white adipose tissue, consistent with reduced energy expenditure. HiFAT feeding also resulted in major decreases in basal and insulin-stimulated conversion of glucose to lipid in liver (26-60%) and brown adipose tissue (88-90%) with relatively less effect in white adipose (0-43%). We conclude that high-fat feeding results in insulin resistance due mainly to effects in oxidative skeletal muscle and BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucagon stimulation of brown adipose tissue growth and thermogenesis

1987 ◽  
Vol 252 (1) ◽  
pp. R160-R165 ◽  
Author(s):  
C. J. Billington ◽  
T. J. Bartness ◽  
J. Briggs ◽  
A. S. Levine ◽  
J. E. Morley
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Lipoprotein Lipase ◽  
Mitochondrial Protein ◽  
Tissue Growth ◽  
Whole Body ◽  
Control Group ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Despite long-standing observations of a whole-body thermogenic effect of glucagon, the role of glucagon in activating thermogenesis in brown adipose tissue has not often been studied. We investigated the ability of administered glucagon to produce alterations in brown adipose tissue similar to changes produced by accepted stimuli of brown fat activity: cold, norepinephrine, and overfeeding. Eighteen days of glucagon injections (1 mg/kg) to male Sprague-Dawley rats produced, relative to saline-injected controls, decreases in feed efficiency and increases in brown adipose tissue weight, protein content, DNA content, and mitochondrial mass as reflected in cytochrome oxidase activity. The observed changes were similar, though of lesser magnitude, to changes produced in these same parameters induced by administration of norepinephrine (250 micrograms/kg) for a positive control group. Four days of glucagon administration (1 mg/kg) produced increases in specific activity of cytochrome oxidase and lipoprotein lipase. After 8 days of glucagon administration, changes in whole-pad activity similar to those seen with 18 days of administration were present. Glucagon also increased whole-pad lipoprotein lipase activity after 4 and 8 days. Surgically denervated interscapular brown adipose tissue retained its ability to respond to exogenous glucagon, though the magnitude of the response was diminished. Guanosine 5'-diphosphate (GDP) binding to brown adipose tissue mitochondria was measured as an assessment of functional state after 5 days of glucagon (1 mg/kg). There was an increase in GDP binding relative to controls whether expressed as picomoles per milligram mitochondrial protein or nanomoles per pad.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonshivering thermogenesis without interscapular brown adipose tissue involvement during conditioned fear in the rat

2009 ◽  
Vol 296 (4) ◽  
pp. R1239-R1247 ◽  
Author(s):  
Andrew Marks ◽  
Daniel M. L. Vianna ◽  
Pascal Carrive
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Conditioned Fear ◽  
Nonshivering Thermogenesis ◽  
Interscapular Brown Adipose Tissue ◽  
Warm Up ◽  
Induced Hyperthermia ◽  
Adrenoceptor Antagonist ◽  
Brown Adipose ◽  
The Difference

As with other forms of psychological stress, conditioned fear causes an increase in body temperature. The mechanisms underlying this stress-induced hyperthermia are not well understood, but previous research suggests that nonshivering thermogenesis might contribute, as it does during cold exposure. The major source of nonshivering thermogenesis in the rat is brown adipose tissue (BAT), and the largest BAT deposit in that species is in the interscapular area just below the skin. BAT is also under sympathetic control via β-adrenoceptors. If BAT contributes to fear-induced hyperthermia, then the interscapular skin should warm up faster than other skin areas, and this response should be suppressed by the β-adrenoceptor antagonist, propranolol. We tested this noninvasively by infrared thermography. In conscious rats, 30 min of contextual fear caused hyperthermia (as indicated by a +1.5°C increase in lumbar back skin temperature) and increased the difference in temperature between interscapular and lumbar back skin (TiScap − TBack) by +1°C. Propranolol (10 mg/kg ip) completely abolished this hyperthermia; however, the TiScap-TBack increase was not reduced. In contrast, exposure to cold air (4°C) induced a +2.7°C increase in TiScap-TBack, which was reduced to +1°C after propranolol. The results show that conditioned fear-induced hyperthermia is of nonshivering origin and mediated by β-adrenoceptors, but interscapular BAT does not contribute to it and does not appear to be activated, either.

High plasma insulin-like growth factor-II and low lipid content in transgenic mice: measurements of lipid metabolism

1994 ◽  
Vol 143 (3) ◽  
pp. 433-439 ◽  
Author(s):  
T H M Da Costa ◽  
D H Williamson ◽  
A Ward ◽  
P Bates ◽  
R Fisher ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Brown Adipose Tissue ◽  
Lipid Content ◽  
Whole Body ◽  
Insulin Like Growth Factor ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Factor Ii

Abstract Transgenic mice were made by introducing extra copies of the mouse insulin-like growth factor-II (IGF-II) gene driven by the bovine keratin 10 promoter (BKVI). The adult plasma IGF-II levels were elevated at least three times in one line. In this line, there was a lower lipid content of both brown and white adipose depots at 2–4 months of age, and 40% less fat in the carcass at 7–9 months. The low lipid phenotype was not detected in the carcass at 2 weeks after birth. The lean characteristic was attributed to circulating IGF-II because the transgene was not expressed in fat. At 2–4 months of age, the transgenes oxidized more oral lipid, and less of this lipid was incorporated into the whole body and the epididymal fat. In contrast, the interscapular brown adipose tissue maintained lipid incorporation and lipoprotein lipase activity despite its reduced size. The altered activity of the brown adipose tissue may account for the gradual onset and persistence of the lean feature of the transgenic mice. There were no substantial changes in lipogenesis which could account for the low fat content. The plasma levels of IGF-I, insulin, glycerol, non-esterified fatty acids, triacylglycerols and glucose were not greatly changed and the pituitary GH content was within the normal range. Journal of Endocrinology (1994) 143, 433–439

Effects of 2-deoxy-D-glucose on sympathetic nerve activity to interscapular brown adipose tissue

1989 ◽  
Vol 257 (6) ◽  
pp. R1377-R1385 ◽  
Author(s):  
M. Egawa ◽  
H. Yoshimatsu ◽  
G. A. Bray
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Sympathetic Activity ◽  
Suppressive Effect ◽  
Cerebral Ventricle ◽  
Neural Activation ◽  
Central Administration ◽  
Interscapular Brown Adipose Tissue ◽  
The Third ◽  
Brown Adipose

The effects on firing rate of sympathetic nerves to interscapular brown adipose tissue were measured after induction of intracellular glycopenia by peripheral or central administration of 2-deoxy-D-glucose (2-DG). Injection of 2-DG (250 mg/kg body wt) into the jugular vein rapidly suppressed the sympathetic activity, which declined 84% within 10 min after the injection. This suppression persisted for at least 40 min. Hyperglycemia did not affect the sympathetic activity but partially inhibited the suppressive effect of 2-DG injection. Acute vagotomy failed to block the suppressive effect of 2-DG. Injection of 2-DG (2.5 mg/rat) into the third cerebral ventricle suppressed the sympathetic activity. This suppression was followed by gradual recovery. Saline injection did not affect the sympathetic activity. We conclude that cellular glycopenia induced by injecting 2-DG peripherally or into the third cerebral ventricle suppresses the sympathetic activity to brown adipose tissue. The results are consistent with the hypothesis that an acute energy shortage decreases the thermogenesis in interscapular brown adipose tissue by suppressing sympathetic neural activation of this tissue.

scholarly journals Brown Adipose Tissue, Whole-Body Energy Expenditure, and Thermogenesis in Healthy Adult Men

Obesity ◽  
2011 ◽  
Vol 19 (1) ◽  
pp. 13-16 ◽  
Author(s):  
Takeshi Yoneshiro ◽  
Sayuri Aita ◽  
Mami Matsushita ◽  
Toshimitsu Kameya ◽  
Kunihiro Nakada ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Healthy Adult ◽  
Whole Body ◽  
Adult Men ◽  
Brown Adipose ◽  
Body Energy

Contribution of brown adipose tissue to central PGE1-evoked hyperthermia in rats

1991 ◽  
Vol 260 (1) ◽  
pp. R59-R66 ◽  
Author(s):  
D. M. Fyda ◽  
K. E. Cooper ◽  
W. L. Veale
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Adipose Tissue ◽  
Systolic Blood Pressure ◽  
Brown Adipose Tissue ◽  
Core Temperature ◽  
Tissue Temperature ◽  
Whole Body ◽  
Central Administration ◽  
Brown Adipose

The relative contribution of several effector systems to a prostaglandin E1-(PGE1) evoked hyperthermia was examined. Infusion of 150 ng of PGE1 into a lateral cerebral ventricle increased core temperature and whole body metabolic rate, brown adipose tissue temperature, systolic blood pressure, and heart rate. Pretreating the animals with a nonselective beta-antagonist propranolol (1 mg/kg iv in 0.3 ml followed by 3 mg.kg-1.h-1 in 0.3 ml/h) not only attenuated the rise in metabolism observed after the central administration of 150 ng PGE1 but also diminished the elevation in both core and brown fat tissue temperatures as well as the increase in heart rate. Pretreating the animals with the alpha-antagonist prazosin (2 mg/kg im followed by 50 micrograms.kg-1.h-1 iv in 0.3 ml/h) somewhat reduced the rise in whole body metabolism, suppressed the elevation in core temperature, but failed to alter the rise in brown adipose tissue temperature normally seen after the central administration of PGE1. Moreover, both the rise in systolic blood pressure and heart rate were attenuated when the PGE1 administration was preceded by prazosin. These results suggest that brown adipose tissue is an important effector organ responsible for mediating the hyperthermic response observed after the intracerebral injection of PGE1. In addition, the results indicate that alterations in vasomotor tone may also be important in producing or sustaining the elevated core temperature found after a pyrogen administration.

The central administration of C75, a fatty acid synthase inhibitor, activates sympathetic outflow and thermogenesis in interscapular brown adipose tissue

2013 ◽  
Vol 465 (12) ◽  
pp. 1687-1699 ◽  
Author(s):  
Priscila Cassolla ◽  
Ernane Torres Uchoa ◽  
Frederico Sander Mansur Machado ◽  
Juliana Bohnen Guimarães ◽  
Maria Antonieta Rissato Garófalo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Sympathetic Outflow ◽  
Central Administration ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Synthase Inhibitor

scholarly journals AN UPDATE ON BROWN ADIPOSE TISSUE BIOLOGY: A DISCUSSION OF RECENT FINDINGS

2021 ◽  
Author(s):  
Rafael Calais Gaspar ◽  
José R Pauli ◽  
Gerald I Shulman ◽  
Vitor Rosetto Muñoz
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Fat Metabolism ◽  
Whole Body ◽  
Potential Treatment ◽  
White Adipocytes ◽  
Tissue Biology ◽  
Brown Adipose ◽  
Distinct Features

Brown adipose tissue (BAT) has been encouraged as a potential treatment for obesity and comorbidities due to its thermogenic activity capacity and contribution to energy expenditure. Some interventions such as cold and β-adrenergic drugs are able to activate BAT thermogenesis as well as promote differentiation of white adipocytes into brown-like cells (browning), enhancing the thermogenic activity of these cells. In this mini-review we discuss new mechanisms related to BAT and energy expenditure. In this regard, we will also discuss recent studies that have revealed the existence of important secretory molecules from BAT "batokines" that act in autocrine, paracrine, and endocrine mechanisms, which in turn may explain some of the beneficial roles of BAT on whole-body glucose and fat metabolism. Finally, we will discuss new insights related to BAT thermogenesis with an additional focus on the distinct features of BAT metabolism between rodents and humans.

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