scholarly journals Fatty Acids Rescue the Thermogenic Function of Sympathetically Denervated Brown Fat

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1428
Author(s):  
Qiang Cao ◽  
Shirong Wang ◽  
Huan Wang ◽  
Xin Cui ◽  
Jia Jing ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Temperature ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Brown Fat ◽  
Key Factors ◽  
Uncoupling Protein 1 ◽  
Physiological Factors ◽  
Brown Adipose

Sympathetic nervous system (SNS) innervation into brown adipose tissue (BAT) has been viewed as an impetus for brown fat thermogenesis. However, we surprisingly discovered that BAT SNS innervation is dispensable for mice to maintain proper body temperature during a prolonged cold exposure. Here we aimed to uncover the physiological factors compensating for maintaining brown fat thermogenesis in the absence of BAT innervation. After an initial decline of body temperature during cold exposure, mice with SNS surgical denervation in interscapular BAT gradually recovered their temperature comparable to that of sham-operated mice. The surgically denervated BAT also maintained a sizable uncoupling protein 1 (UCP1) protein along with basal norepinephrine (NE) at a similar level to that of sham controls, which were associated with increased circulating NE. Furthermore, the denervated mice exhibited increased free fatty acid levels in circulation. Indeed, surgical denervation of mice with CGI-58 deletion in adipocytes, a model lacking lipolytic capacity to release fatty acids from WAT, dramatically reduced BAT UCP1 protein and rendered the mice susceptible to cold. We conclude that circulating fatty acids and NE may serve as key factors for maintaining BAT thermogenic function and body temperature in the absence of BAT sympathetic innervation.

scholarly journals Pyruvate induces torpor in obese mice

2018 ◽  
Vol 115 (4) ◽  
pp. 810-815 ◽  
Author(s):  
Marion Soto ◽  
Lucie Orliaguet ◽  
Michelle L. Reyzer ◽  
M. Lisa Manier ◽  
Richard M. Caprioli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Metabolic Rate ◽  
Brown Adipose Tissue ◽  
Mass Spectroscopy ◽  
Uncoupling Protein ◽  
Obese Mice ◽  
Uncoupling Protein 1 ◽  
Metabolic Intermediate ◽  
Brown Adipose

Mice subjected to cold or caloric deprivation can reduce body temperature and metabolic rate and enter a state of torpor. Here we show that administration of pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with diet-induced or genetic obesity. This is associated with marked hypothermia, decreased activity, and decreased metabolic rate. The drop in body temperature correlates with the degree of obesity and is blunted by housing mice at thermoneutrality. Induction of torpor by pyruvate in obese mice relies on adenosine signaling and is accompanied by changes in brain levels of hexose bisphosphate and GABA as detected by mass spectroscopy-based imaging. Pyruvate does not induce torpor in lean mice but results in the activation of brown adipose tissue (BAT) with an increase in the level of uncoupling protein-1 (UCP1). Denervation of BAT in lean mice blocks this increase in UCP1 and allows the pyruvate-induced torpor phenotype. Thus, pyruvate administration induces torpor in obese mice by pathways involving adenosine and GABA signaling and a failure of normal activation of BAT.

scholarly journals Programming mediated by fatty acids affects uncoupling protein 1 (UCP-1) in brown adipose tissue

2018 ◽  
Vol 120 (6) ◽  
pp. 619-627 ◽  
Author(s):  
Perla P. Argentato ◽  
Helena de Cássia César ◽  
Débora Estadella ◽  
Luciana P. Pisani
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Dietary Fatty Acids ◽  
Research Trend ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Pregnancy And Lactation ◽  
The Impact

AbstractBrown adipose tissue (BAT) has recently been given more attention for the part it plays in obesity. BAT can generate great amounts of heat through thermogenesis by the activation of uncoupling protein 1 (UCP-1), which can be regulated by many environmental factors such as diet. Moreover, the build-up of BAT relates to maternal nutritional changes during pregnancy and lactation. However, at present, there is a limited number of studies looking at maternal nutrition and BAT development, and it seems that the research trend in this field has been considerably declining since the 1980s. There is much to discover yet about the role of different fatty acids on the development of BAT and the activation of UCP-1 during the fetal and the postnatal periods of life. A better understanding of the impact of nutritional intervention on the epigenetic regulation of BAT could lead to new preventive care for metabolic diseases such as obesity. It is important to know in which circumstances lipids could programme BAT during pregnancy and lactation. The modification of maternal dietary fatty acids, amount and composition, during pregnancy and lactation might be a promising strategy for the prevention of obesity in the offspring and future generations.

scholarly journals Cold acclimation enhances UCP1 content, lipolysis, and triacylglycerol resynthesis, but not mitochondrial uncoupling and fat oxidation, in rat white adipocytes

2019 ◽  
Vol 316 (3) ◽  
pp. C365-C376 ◽  
Author(s):  
Diane M. Sepa-Kishi ◽  
Shailee Jani ◽  
Daniel Da Eira ◽  
Rolando B. Ceddia
Keyword(s):  
Fatty Acids ◽  
Cold Acclimation ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Uncoupling Protein ◽  
Fat Oxidation ◽  
Uncoupling Protein 1 ◽  
Mitochondrial Uncoupling ◽  
Palmitate Oxidation ◽  
White Adipocytes ◽  
Brown Adipose

The objective of this study was to investigate whether cold-induced browning of the subcutaneous (Sc) inguinal (Ing) white adipose tissue (WAT) increases the capacity of this tissue to oxidize fatty acids through uncoupling protein 1 (UCP1)-mediated thermogenesis. To accomplish that, rats were acclimated to cold (4°C for 7 days). Subsequently, interscapular and aortic brown adipose tissues (iBAT and aBAT, respectively), epididymal (Epid), and Sc Ing WAT were used for adipocyte isolation. In BAT adipocytes, cold acclimation increased UCP1 content and palmitate oxidation either in the absence or presence of oligomycin, whereas in Sc Ing adipocytes glucose and palmitate oxidation were not affected, although multilocular adipocytes were formed and UCP1 content increased upon cold acclimation in the WAT. Furthermore, isoproterenol-stimulated cold Sc Ing adipocytes exhibited significantly lower rates of palmitate oxidation than control cells when exposed to oligomycin. These findings provide evidence that, despite increasing UCP1 levels, cold acclimation essentially reduced mitochondrial uncoupling-mediated fat oxidation in Sc Ing adipocytes. Conversely, glycerol kinase and phosphoenolpyruvate carboxykinase levels, isoproterenol-induced lipolysis, as well as glycerol and palmitate incorporation into lipids significantly increased in these cells. Therefore, instead of UCP1-mediated mitochondrial uncoupling, cold acclimation increased the capacity of Sc Ing adipocytes to export fatty acids and enhanced key components of the triacylglycerol resynthesis pathway in the Sc Ing WAT.

scholarly journals Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria

2015 ◽  
Vol 90 (5) ◽  
pp. 1117-1128 ◽  
Author(s):  
Irina G. Shabalina ◽  
Anastasia V. Kalinovich ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Fatty Acids ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Uncoupling Protein 1 ◽  
Brown Fat Mitochondria

scholarly journals Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice

2020 ◽  
Vol 61 (11) ◽  
pp. 1377-1389 ◽  
Author(s):  
Alexander W. Fischer ◽  
Janina Behrens ◽  
Frederike Sass ◽  
Christian Schlein ◽  
Markus Heine ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Surrogate Marker ◽  
Glucose Disposal ◽  
Uncoupling Protein 1 ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Deficient Mice

Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of 18F-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with β-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP1-mediated thermogenesis. In metabolic studies using radiolabeled tracers, we found that glucose uptake is increased in mildly cold-activated BAT of Ucp1−/− versus WT mice kept at subthermoneutral temperature. Conversely, lower glucose disposal was detected after full thermogenic activation achieved by sustained cold exposure or CL treatment. In contrast, uptake of lipoprotein-derived fatty acids into chronically activated thermogenic adipose tissues was substantially increased in UCP1-deficient mice. This effect is linked to higher sympathetic tone in adipose tissues of Ucp1−/− mice, as indicated by elevated levels of thermogenic genes in BAT and WAT. Thus, glucose and lipoprotein handling does not necessarily reflect UCP1-dependent thermogenic activity, but especially lipid uptake rather mirrors sympathetic activation of adipose tissues.

scholarly journals Modulation of uncoupling protein 2 and uncoupling protein 3: regulation by denervation, leptin and retinoic acid treatment

2000 ◽  
Vol 164 (3) ◽  
pp. 331-337 ◽  
Author(s):  
PJ Scarpace ◽  
M Matheny ◽  
RL Moore ◽  
MV Kumar
Keyword(s):  
Retinoic Acid ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Sympathetic Stimulation ◽  
Uncoupling Protein 1 ◽  
Adrenergic Agonist ◽  
Uncoupling Protein 3 ◽  
Brown Adipose ◽  
Cgp 12177 ◽  
Ucp2 Mrna

We recently reported that the leptin-induced increase in uncoupling protein 1 (UCP1) mRNA in brown adipose tissue (BAT) is prevented by the denervation of BAT. We also reported that retinoic acid (RA) increases UCP1 mRNA in BAT. To extend these finding to UCP2 and UCP3 in BAT, we examined UCP2 and UCP3 mRNA after unilateral denervation of BAT, as well as after leptin, beta(3)-adrenergic agonist, RA, and glucocorticoid administration to rats. UCP3 mRNA was 20% less in the denervated compared with the intact BAT, whereas UCP2 mRNA was unchanged with denervation. The beta(3)-adrenergic agonist, CGP-12177 (0.75 mg/kg), increased UPC3 mRNA by 40% in the innervated and by 85% in the denervated BAT. Leptin (0.9 mg/day for 3 days) increased both UCP2 and UCP3 mRNA by 30% in the innervated and, surprisingly, in the denervated BAT. RA (7.5 mg/kg) increased UCP1 mRNA but decreased UCP2 and UCP3 mRNA by 50%, whereas methylprednisolone (65 mg/kg, two doses 24 h apart) suppressed all three uncoupling proteins by greater than 60%. The present findings indicate that: sympathetic innervation is necessary to maintain basal levels of UCP3 mRNA; beta(3)-adrenergic agonist stimulation induces UCP3 mRNA; leptin induces UCP2 and UCP3 mRNA and this induction is not dependent on sympathetic innervation; RA increases UCP1 but decreases UCP2 and UCP3 mRNA; and methylprednisolone suppresses UCP1, UCP2, and UCP3 mRNA equally. These data suggest that there are distinct patterns of regulation between UCP1, UCP2, and UCP3, and there may be at least two modes by which leptin could modulate thermogenesis in BAT; first, by increasing sympathetic stimulation of BAT and induction of UCP1 mRNA and, secondly, by increasing UCP2 and UCP3 mRNA by a mechanism independent of sympathetic stimulation.

Hyperphagia in cold-exposed rats is accompanied by decreased plasma leptin but unchanged hypothalamic NPY

1998 ◽  
Vol 274 (1) ◽  
pp. R62-R68 ◽  
Author(s):  
Chen Bing ◽  
Helen M. Frankish ◽  
Lucy Pickavance ◽  
Qiong Wang ◽  
David F. C. Hopkins ◽  
...  
Keyword(s):  
Food Intake ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Sympathetic Outflow ◽  
Uncoupling Protein 1 ◽  
Bat Activity ◽  
Fat Mobilization ◽  
Brown Adipose ◽  
Plasma Leptin ◽  
Lethal Hypothermia

Chronic cold exposure stimulates sympathetically driven thermogenesis in brown adipose tissue (BAT), resulting in fat mobilization, weight loss, and compensatory hyperphagia. Hypothalamic neuropeptide Y (NPY) neurons are implicated in stimulating food intake in starvation, but may also suppress sympathetic outflow to BAT. This study investigated whether the NPY neurons drive hyperphagia in rats that have lost weight through cold exposure. Rats exposed to 4°C for 21 days weighed 14% less than controls maintained at 22°C ( P < 0.001). Food intake increased after 3 days and remained 10% higher thereafter ( P < 0.001). Increased BAT activity was confirmed by 64, 96, and 335% increases in uncoupling protein-1 mRNA at 2, 8, and 21 days. Plasma leptin decreased during prolonged cold exposure. Cold-exposed rats showed no significant changes in NPY concentrations in any hypothalamic regions or in hypothalamic NPY mRNA at any time. We conclude that the NPY neurons are not activated during cold exposure. This is in contrast with starvation-induced hyperphagia, but is biologically appropriate since enhanced NPY release would inhibit thermogenesis causing potentially lethal hypothermia. Other neuronal pathways must therefore mediate hyperphagia in chronic cold exposure.

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