Thermogenic capacity and brown fat in rats exercise-trained by running

doi:10.1016/0026-0495(87)90067-9

Metabolism

Volume 36, Issue 1, January 1987, Pages 76-81

https://doi.org/10.1016/0026-0495(87)90067-9 Get rights and content

Abstract

Brown adipose tissue, a major effector of nonshivering thermogenesis (NST) in mammals, is activated by the sympathetic neurotransmitter norepinephrine. Prolonged increases in norepinephrine levels, whether elicited by cold exposure or exogenous application of catecholamines, lead to increased NST and increased thermogenic capacity of brown fat. Exercise training is also accompanied by enhanced sympathetic activity. The possibility exists that this enhancement may alter brown fat function. The present study was designed to assess the effect of a running exercise regimen on whole animal NST and the in vivo response of brown fat. Rats were trained by running on a treadmill (an average of 17 m/min, 0° incline, for 90 min/d) for a period of at least 6 weeks. Whole animal NST capacity was assessed by monitoring oxygen consumption in response to infusion of norepinephrine. As a measure of the contribution of brown fat to whole body NST, the mass and norepinephrine-stimulated blood flow (microsphere technique) to the tissue were measured. None of these variables differed between the exercised (n = 10) and sedentary (n = 10) groups. That is, there were no significant differences between the two groups with respect to resting oxygen consumption, norepinephrine-induced oxygen consumption, brown fat mass, and brown fat blood flow—whether expressed per gram of tissue or as total tissue blood flow (ie, tissue mass × blood flow per gram). Further study is needed to explain the differential responses of brown fat to the increased sympathetic activity occurring during exercise v that occurring during cold exposure.

References (41)

BA Horwitz
Neurohumoral regulation of nonshivering thermogenesis in mammals
J Hudson
Torpidity in mammals
G Mory et al.
Noradrenaline controls the concentration of the uncoupling protein in brown adipose tissue
FEBS Lett
(1984)
QR Rogers et al.
Amino acid diets and maximal growth in the rat
J Nutr
(1965)
EA Applegate et al.
Food intake, body composition and blood lipids following treadmill exercise in male and female rats
Physiol Behav
(1982)
G Heldmaier
Relationship between nonshivering thermogenesis and body size
RE Smith et al.
Brown fat and thermogenesis
Physiol Rev
(1969)
DO Foster et al.
Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline
Can J Physiol Pharmacol
(1978)
L Jansky
Nonshivering thermogenesis and its thermoregulatory significance
Biol Rev
(1973)
IL Cameron et al.
Cytological responses of brown fat tissue in cold-exposed rats
J Cell Biol
(1964)

J Himms-Hagen

Cellular thermogenesis

Annu Rev Physiol

(1976)

J Himms-Hagen

Brown adipose tissue metabolism and thermogenesis

Annu Rev Nutr

(1985)

S Wickler

Seasonal changes in enzymes of aerobic heat production in the white footed mouse

Am J Physiol

(1981)

DO Foster et al.

Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats reevaluated from changes in tissue blood flow: The dominant role of brown adipose tissue in the replacement of shivering by nonshivering thermogenesis

Can J Physiol Pharmacol

(1979)

DO Foster et al.

Noradrenaline-induced calorigenesis in warm- and cold-acclimated rats: Relations between concentrations of noradrenaline in arterial plasma, blood flow to differently located masses of brown adipose tissue, and calorigenic response

Can J Physiol Pharmacol

(1980)

J LeBlanc et al.

Importance of noradrenaline in cold adaptation

Am J Physiol

(1964)

I Ostman-Smith

Adaptive changes in the sympathetic nervous system and some effector organs of the rat following low term exercise or cold acclimation and the role of cardiac sympathetic nerves in the genesis of compensatory cardiac hypertrophy

Acta Physiol Scand

(1979)

K Hirata et al.

Enhancement of calorigenic response to cold and to norepinephrine in physically trained rats

Jpn J Physiol

(1981)

K Hirata

Blood flow to brown adipose tissue and norepinephrine-induced calorigenesis in physically trained rats

Jpn J Physiol

(1982)

J LeBlanc et al.

Effect of diet and exercise on norepinephrine-induced thermogenesis in male and female rats

J Appl Physiol

(1982)

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The purpose of this study was to investigate whether there is an interacting effect of six weeks of swimming in cold water on the gene expression of browning markers in adipose tissue in rodents. Twenty male Wistar rats were randomly divided into four groups: Control (C, 25 °C), Cold Exposure (CE, 4 °C), Swimming in tepid Water (STW, 30 °C), and Swimming in Cold Water (SCW, 15 °C). The swimming included 2–3 min intervals, 1 min rest, until exhaustion, three days a week for six weeks, with 3 to 6% of bodyweight overload. Rats from CE were exposed to cold for 2 h per day, five days per week. After the experimental protocol, interscapular brown (BAT) and inguinal subcutaneous white (WAT) fat tissues were excised, weighed, and processed for beiging and mitochondrial biogenesis markers gene expression. The experimental protocols resulted in an apparent increase in the number of brown adipocytes (per mm²) in the adipose deposits compared to the C group; substantial changes were observed in the SCW group. Compared to other groups, cold exposure alone increased significantly serum norepinephrine, and also β₂-adrenergic receptor expression was upregulated in the adipocytes compared to the C group. The STW group increased the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1 alpha (PGC-1α), β₂-adrenergic receptor, and CCAAT/enhancer-binding proteins-α(c/EBP-α) in WAT in comparison with the C group(p < 0.05). In both adipocytes, the SCW intervention significantly upregulated the expression of PGC-1α, PPAR-γ, and c/EBP-α genes in comparison with the C and CE groups. In addition, the expression of TFAM and UCP1 was upregulated substantially in the SCW group compared to other groups. Our data demonstrate that swim training and cold exposure present additive effects in the expression of genes involved in the beiging process and mitochondrial biogenesis markers in BAT and WAT. In addition, it seems that the upregulation of these genes is related to the activation of β₂-adrenergic receptors.
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Currently, a randomized controlled trial in young sedentary adults has revealed that 24-week exercise intervention does not affect BAT volume and activity as evaluated by 18F-fluorodeoxyglucose uptake into BAT [20]. However, in the rodent studies, the effects of exercise training on mitochondrial content or activity in BAT remain controversial; some studies have suggested that mitochondrial activity increased [31–33], decreased [34], or did not change [35–37] in the BAT with exercise training. BAT thermogenic activity is influenced by the activation of the sympathetic nervous system.
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Fatty acid activation in thermogenic adipose tissue
2019, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
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To that effect, physical exercise has been proposed to promote WAT browning. Whereas the effect of exercise on BAT activity is controversial [114–118], several reports in rodents suggest that exercise results in increased browning of WAT [119–123]. Although it is surprising that exercise, an energy-consuming process, would induce the transformation of cells that inherently increase energy expenditure, one possible explanation is that the exercise-induced decrease in fat mass may necessitate an increased heat production to facilitate the insulation of the body [124].
Channeling carbohydrates and fatty acids to thermogenic tissues, including brown and beige adipocytes, have garnered interest as an approach for the management of obesity-related metabolic disorders. Mitochondrial fatty acid oxidation (β-oxidation) is crucial for the maintenance of thermogenesis. Upon cellular fatty acid uptake or following lipolysis from triglycerides (TG), fatty acids are esterified to coenzyme A (CoA) to form active acyl-CoA molecules. This enzymatic reaction is essential for their utilization in β-oxidation and thermogenesis. The activation and deactivation of fatty acids are regulated by two sets of enzymes called acyl-CoA synthetases (ACS) and acyl-CoA thioesterases (ACOT), respectively. The expression levels of ACS and ACOT family members in thermogenic tissues will determine the substrate availability for β-oxidation, and consequently the thermogenic capacity. Although the role of the majority of ACS and ACOT family members in thermogenesis remains unclear, recent proceedings link the enzymatic activities of ACS and ACOT family members to metabolic disorders and thermogenesis. Elucidating the contributions of specific ACS and ACOT family members to trafficking of fatty acids towards thermogenesis may reveal novel targets for modulating thermogenic capacity and treating metabolic disorders.
Lipidomic Adaptations in White and Brown Adipose Tissue in Response to Exercise Demonstrate Molecular Species-Specific Remodeling
2017, Cell Reports
Citation Excerpt :
From a biological perspective, it is possible that exercise-induced β-adrenergic receptor stimulation results in activation of BAT and stimulation of lipolysis, although this has not been clearly established. In fact, the effects of exercise on gene expression and metabolic activity in BAT have resulted in conflicting observations; some studies have demonstrated increased BAT activity with exercise (Hirata, 1982; Hirata and Nagasaka, 1981; Ignacio et al., 2012; Xu et al., 2011a, 2011b; Yoshioka et al., 1989), others studies showed no exercise-induced changes in BAT activity (Leblanc et al., 1982; Richard et al., 1986, 1987; Wickler et al., 1987), and another set of studies reported a decrease in BAT activity with exercise (Boss et al., 1998; Larue-Achagiotis et al., 1994; Stanford and Goodyear, 2016; Sullo et al., 2004; Vosselman et al., 2015; Wu et al., 2014). Although the effects of exercise on BAT are unclear, both WAT and BAT can regulate fatty acid homeostasis in addition to glucose metabolism (Chondronikola et al., 2014; Stanford et al., 2013, 2015b).
Exercise improves whole-body metabolic health through adaptations to various tissues, including adipose tissue, but the effects of exercise training on the lipidome of white adipose tissue (WAT) and brown adipose tissue (BAT) are unknown. Here, we utilize MS/MS^ALL shotgun lipidomics to determine the molecular signatures of exercise-induced adaptations to subcutaneous WAT (scWAT) and BAT. Three weeks of exercise training decrease specific molecular species of phosphatidic acid (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS) in scWAT and increase specific molecular species of PC and PE in BAT. Exercise also decreases most triacylglycerols (TAGs) in scWAT and BAT. In summary, exercise-induced changes to the scWAT and BAT lipidome are highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflect selective remodeling in scWAT and BAT of both phospholipids and glycerol lipids in response to exercise training, thus providing a comprehensive resource for future studies of lipid metabolism pathways.
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2015, Contemporary Clinical Trials
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Of interest is that both SNS and non-SNS BAT activators are sensitive to exercise [22,23]. Several studies conducted in animal models have reported an increased BAT activity and browning after an exercise-based intervention [18,24–27], yet there is still some controversy [28–32]. In humans, there seem to exist a positive association of exercise with BAT and browning activity [33–35].
The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise. ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes).
ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18–25 years. Eligible participants will be randomly assigned to a non-exercise group (n ≈ 50) or one of two exercise groups (n = 50 each). Participants in the exercise groups will perform aerobic and strength training 3–4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70% RM for the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery.
Findings from ACTIBATE will have significant implications for our understanding of exercise and its protective effects against the development of type 2 diabetes, obesity and related metabolic diseases.
ClinicalTrials.gov ID: NCT02365129
Energy dissipation in brown adipose tissue: From mice to men
2013, Molecular and Cellular Endocrinology
Citation Excerpt :
In the past decades, several animal studies have investigated whether exercise has beneficial effects on BAT activity and recruitment. It was hypothesized that exercise could affect BAT function via the SNS, as exercise is known to increase general SNS activity (Wickler et al., 1987). However, most studies did not find any stimulatory effect of exercise on BAT activity (Scarpace et al., 1994; Segawa et al., 1998; Shibata and Nagasaka, 1987; Wickler et al., 1987), except for studies using swimming exercise protocols (Hirata, 1982a,b; Oh-ishi et al., 1996), which probably induced BAT activity to compensate for the heat loss to the water.
In rodents, brown adipose tissue (BAT) is a metabolic organ that produces heat in response to cold and dietary intake through mitochondrial uncoupling. For long time, BAT was considered to be solely important in small mammals and infants, however recent studies have shown that BAT is also functional in adult humans. Interestingly, the presence and/or functionality of this thermogenic tissue is diminished in obese people, suggesting a link between human BAT and body weight regulation. In the last years, evidence has also emerged for the existence of adipocytes that may have an intermediate thermogenic phenotype between white and brown adipocytes, so called brite or beige adipocytes. Together, these findings have resulted in a renewed interested in (human) brown adipose tissue and pathways to increase the activity and recruitment of these thermogenic cells. Stimulating BAT hypertrophy and hyperplasia in humans could be a potential strategy to target obesity. Here we will review suggested pathways leading to BAT activation in humans, and discuss novel putative BAT activators in rodents into human perspective.

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^☆: Supported in part by NIH Grants AM-18899 and AM-27019 and a grant from the Agricultural Research Service of the USDA (agreement 58-91H2-6-34).

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Thermogenic capacity and brown fat in rats exercise-trained by running☆

Abstract

FEBS Lett

J Nutr

Physiol Behav

Relationship between nonshivering thermogenesis and body size

Brown fat and thermogenesis

Physiol Rev

Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline

Can J Physiol Pharmacol

Nonshivering thermogenesis and its thermoregulatory significance

Biol Rev

Cytological responses of brown fat tissue in cold-exposed rats

J Cell Biol

Cellular thermogenesis

Annu Rev Physiol

Brown adipose tissue metabolism and thermogenesis

Annu Rev Nutr

Seasonal changes in enzymes of aerobic heat production in the white footed mouse

Am J Physiol

Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats reevaluated from changes in tissue blood flow: The dominant role of brown adipose tissue in the replacement of shivering by nonshivering thermogenesis

Can J Physiol Pharmacol

Noradrenaline-induced calorigenesis in warm- and cold-acclimated rats: Relations between concentrations of noradrenaline in arterial plasma, blood flow to differently located masses of brown adipose tissue, and calorigenic response

Can J Physiol Pharmacol

Importance of noradrenaline in cold adaptation

Am J Physiol

Adaptive changes in the sympathetic nervous system and some effector organs of the rat following low term exercise or cold acclimation and the role of cardiac sympathetic nerves in the genesis of compensatory cardiac hypertrophy

Acta Physiol Scand

Enhancement of calorigenic response to cold and to norepinephrine in physically trained rats

Jpn J Physiol

Blood flow to brown adipose tissue and norepinephrine-induced calorigenesis in physically trained rats

Jpn J Physiol

Effect of diet and exercise on norepinephrine-induced thermogenesis in male and female rats

J Appl Physiol