scholarly journals Biomarkers of Browning in Cold Exposed Siberian Adults

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2162
Author(s):  
Agrafena Efremova ◽  
Georgia Colleluori ◽  
Mikhail Thomsky ◽  
Jessica Perugini ◽  
Marina Protasoni ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Exposed Group ◽  
Anthropometric Parameters ◽  
Cold Temperatures ◽  
Bat Activity ◽  
Fat Depots ◽  
Brown Adipose ◽  
White Fat

Cold-exposure promotes energy expenditure by inducing brown adipose tissue (BAT) thermogenesis, which over time, is also sustained by browning, the appearance, or increase, of brown-like cells into white fat depots. Identification of circulating markers reflecting BAT activity and browning is crucial to study this phenomenon and its triggers, also holding possible implications for the therapy of obesity and metabolic diseases. Using RT-qPCR, we evaluated the peripheral blood mononuclear cells (PBMC) expression profile of regulators of BAT activity (CIDEA, PRDM16), white adipocytes browning (HOXC9 and SLC27A1), and fatty acid β-oxidation (CPT1A) in 150 Siberian healthy miners living at extremely cold temperatures compared to 29 healthy subjects living in thermoneutral conditions. Anthropometric parameters, glucose, and lipid profiles were also assessed. The cold-exposed group showed significantly lower weight, BMI, hip circumference, and PBMC expression of CIDEA, but higher expression of HOXC9 and higher circulating glucose compared to controls. Within the cold-exposed group, BMI, total cholesterol, and the atherogenic coefficient were lower in individuals exposed to low temperatures for a longer time. In conclusion, human PBMC expresses the brown adipocytes marker CIDEA and the browning marker HOXC9, which, varying according to cold-exposure, possibly reflect changes in BAT activation and white fat browning.

Gene expression of peripheral blood mononuclear cells is affected by cold exposure

2015 ◽  
Vol 309 (8) ◽  
pp. R824-R834 ◽  
Author(s):  
Bàrbara Reynés ◽  
Estefanía García-Ruiz ◽  
Paula Oliver ◽  
Andreu Palou
Keyword(s):  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Cold Exposure ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Fat Depots ◽  
Brown Adipose ◽  
Blood Mononuclear Cells ◽  
Retroperitoneal White Adipose Tissue

Because of the discovery of brown adipose tissue (BAT) in humans, there is increased interest in the study of induction of this thermogenic tissue as a basis to combat obesity and related complications. Cold exposure is one of the strongest stimuli able to activate BAT and to induce the appearance of brown-like (brite) adipocytes in white fat depots (browning process). We analyzed the potential of peripheral blood mononuclear cells (PBMCs) to reflect BAT and retroperitoneal white adipose tissue (rWAT) response to 1-wk cold acclimation (4°C) at different ages of rat development (1, 2, 4, and 6 mo). As expected, cold exposure increased fatty acid β-oxidation capacity in BAT and rWAT (increased Cpt1a expression), explaining increased circulating nonesterified free fatty acids and decreased adiposity. Cold exposure increased expression of the key thermogenic gene, Ucp1, in BAT and rWAT, but only in 1-mo-old animals. Additionally, other brown/brite markers were affected by cold during the whole developmental period studied in BAT. However, in rWAT, cold exposure increased studied markers mainly at early age. PBMCs did not express Ucp1, but expressed other brown/brite markers, which were cold regulated. Of particular interest, PBMCs reflected adipose tissue-increased Cpt1a mRNA expression in response to cold (in older animals) and browning induction occurring in rWAT of young animals (1 mo) characterized by increased Cidea expression and by the appearance of a high number of multilocular CIDE-A positive adipocytes. These results provide evidence pointing to PBMCs as an easily obtainable biological material to be considered to perform browning studies with minimum invasiveness.

scholarly journals Systematic assessment of lipid profiles for the discovery of tissue contributors to the circulating lipid pool in cold exposure

2021 ◽  
Author(s):  
Raghav Jain ◽  
Gina Wade ◽  
Irene Ong ◽  
Bhagirath Chaurasia ◽  
Judith Simcox
Keyword(s):  
Cold Exposure ◽  
Metabolic Diseases ◽  
Plasma Lipids ◽  
Acute Stress ◽  
Plasma Lipid ◽  
Functional Roles ◽  
Systematic Assessment ◽  
Lipid Pool ◽  
Brown Adipose

Plasma lipid levels are altered in chronic conditions such as type 2 diabetes and cardiovascular disease as well as acute stresses such as fasting and cold exposure. Advances in mass spectrometry based lipidomics have uncovered the complexity of the plasma lipidome which includes over 500 lipids that serve functional roles including energy substrate and signaling molecule. The plasma lipid pool is maintained through regulation of tissue production, secretion, and uptake. A major challenge is establishing the tissues of origin and uptake for various plasma lipids, which is necessary to determine the lipid function. Using cold exposure as an acute stress, we performed global lipidomics on the plasma and nine tissues that may contribute to the circulating pool. We found that numerous species of plasma acylcarnitines (ACars) and ceramides were significantly changed with cold exposure. Through computational assessment, we identified the liver and brown adipose tissue (BAT) as major contributors and consumers of circulating ACars, in agreement with our previous work. We further identified the kidney and intestine as novel contributors to the circulating ACar pool and validated these findings with gene expression analysis. Regression analysis also identified that the BAT and kidney as regulators of the plasma ceramide pool. These studies provide an adaptable computational tool to assess tissue contribution to the plasma lipid pool. Our findings have implications in understanding the function of plasma ACars and ceramides, which are elevated in metabolic diseases.

scholarly journals Effects of cold exposure revealed by global transcriptomic analysis in ferret peripheral blood mononuclear cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bàrbara Reynés ◽  
Evert M. van Schothorst ◽  
Jaap Keijer ◽  
Andreu Palou ◽  
Paula Oliver
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Cold Exposure ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Cycle Gene ◽  
Peripheral Blood Mononuclear ◽  
Brown Adipose ◽  
Blood Mononuclear Cells

AbstractAnimal studies, mostly performed in rodents, show the beneficial anti-obesity effects of cold studies. This is due to thermogenic activation of brown adipose tissue (BAT), a tissue also recently discovered in adult humans. Studies in humans, however, are hampered by the accessibility of most tissues. In contrast, peripheral blood mononuclear cells (PBMC) are accessible and share the expression profile of different sets of genes with other tissues, including those that reflect metabolic responses. Ferrets are an animal model physiologically closer to humans than rodents. Here, we investigated the effects on ferrets of one-week acclimation to 4 °C by analysing the PBMC transcriptome. Cold exposure deeply affected PBMC gene expression, producing a widespread down-regulation of genes involved in different biological pathways (cell cycle, gene expression regulation/protein synthesis, immune response, signal transduction, and genes related to extracellular matrix/cytoskeleton), while thermogenic and glycogenolysis-related processes were increased. Results obtained in PBMC reflected those of adipose tissue, but hardly those of the liver. Our study, using ferret as a model, reinforce PBMC usefulness as sentinel biological material for cold-exposure studies in order to deepen our understanding of the general and specific pathways affected by cold acclimation. This is relevant for future development of therapies to be used clinically.

Relation of Diet-Induced Thermogenesis to Brown Adipose Tissue Activity in Healthy Men

2020 ◽  
Author(s):  
Rahel Catherina Loeliger ◽  
Claudia Irene Maushart ◽  
Gani Gashi ◽  
Jaël Rut Senn ◽  
Martina Felder ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Oral Glucose ◽  
Oral Glucose Load ◽  
Glucose Load ◽  
Healthy Men ◽  
Bat Activity ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

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.

scholarly journals Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 388
Author(s):  
Angie S. Xiang ◽  
Corey Giles ◽  
Rebecca K.C. Loh ◽  
Melissa F. Formosa ◽  
Nina Eikelis ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Surrogate Marker ◽  
Omega 3 ◽  
Bat Activity ◽  
Brown Adipose ◽  
Lipid Species

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species—in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.

scholarly journals Melatonin deficiency decreases brown adipose tissue acute thermogenic capacity in rats measured by 18F-FDG PET

2020 ◽  
Author(s):  
Bruno Halpern ◽  
Marcio C Mancini ◽  
Caroline Mendes ◽  
Camila Maria Longo Machado ◽  
Silvana Prando ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mrna Expression ◽  
Cold Exposure ◽  
Fdg Pet ◽  
Room Temperature ◽  
Bat Activity ◽  
Acute Cold Exposure ◽  
Brown Adipose ◽  
Thermogenic Capacity

Abstract Objective: Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasively and. the gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG PET). There is no study, to our knowledge, that has evaluated if melatonin influences BAT activity, measured by this imaging technique in animals. Methods: Three experimental groups of Wistar rats (control, pinealectomy, and pinealectomy replaced with melatonin) had an 18F-FDG PET performed at room temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/room temperature was called “acute thermogenic capacity” (ATC) We also measured UCP-1 mRNA expression to correlate with the 18F-FDG PET results. Results: Pinealectomy led to reduced acute thermogenic capacity, compared with the other groups, as well as reduced UCP1 mRNA expression.Conclusion: Melatonin deficiency impairs BAT response when exposed to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without needing an invasive evaluation of BAT.

scholarly journals Mapping of human brown adipose tissue in lean and obese young men

2017 ◽  
Vol 114 (32) ◽  
pp. 8649-8654 ◽  
Author(s):  
Brooks P. Leitner ◽  
Shan Huang ◽  
Robert J. Brychta ◽  
Courtney J. Duckworth ◽  
Alison S. Baskin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Body Mass ◽  
Cold Exposure ◽  
Young Men ◽  
Total Body Mass ◽  
Fat Depots ◽  
Increase Glucose Uptake ◽  
Brown Adipose ◽  
Wide Range

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1–71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT—cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal—with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

scholarly journals Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation

2019 ◽  
Vol 20 (10) ◽  
pp. 2456 ◽  
Author(s):  
Huanyu Lu ◽  
Shan Tang ◽  
Chong Xue ◽  
Ying Liu ◽  
Jiye Wang ◽  
...  
Keyword(s):  
Cold Stress ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Cold Adaptation ◽  
Therapeutic Strategy ◽  
Erk Signaling ◽  
Lipid Trafficking ◽  
Brown Adipose ◽  
White Fat ◽  
Harsh Conditions

Cold exposure stress causes hypothermia, cognitive impairment, liver injury, and cardiovascular diseases, thereby increasing morbidity and mortality. Paradoxically, cold acclimation is believed to confer metabolic improvement to allow individuals to adapt to cold, harsh conditions and to protect them from cold stress-induced diseases. However, the therapeutic strategy to enhance cold acclimation remains less studied. Here, we demonstrate that the mitochondrial-derived peptide MOTS-c efficiently promotes cold adaptation. Following cold exposure, the improvement of adipose non-shivering thermogenesis facilitated cold adaptation. MOTS-c, a newly identified peptide, is secreted by mitochondria. In this study, we observed that the level of MOTS-c in serum decreased after cold stress. MOTS-c treatment enhanced cold tolerance and reduced lipid trafficking to the liver. In addition, MOTS-c dramatically upregulated brown adipose tissue (BAT) thermogenic gene expression and increased white fat “browning”. This effect might have been mediated by MOTS-c-activated phosphorylation of the ERK signaling pathway. The inhibition of ERK signaling disturbed the up-regulatory effect of MOTS-c on thermogenesis. In summary, our results indicate that MOTS-c treatment is a potential therapeutic strategy for defending against cold stress by increasing the adipose thermogenesis via the ERK pathway.

scholarly journals Paternal hyperglycemia in rats exacerbates the development of obesity in offspring

2017 ◽  
Vol 234 (2) ◽  
pp. 175-186 ◽  
Author(s):  
Xiaoqin Shi ◽  
Xinyu Li ◽  
Yi Hou ◽  
Xuemei Cao ◽  
Yuyao Zhang ◽  
...  
Keyword(s):  
Food Intake ◽  
Cold Exposure ◽  
Metabolic Diseases ◽  
Identical Condition ◽  
Female Rats ◽  
Normal Female ◽  
Citrate Buffer ◽  
Parental History ◽  
Leptin Signaling ◽  
Brown Adipose

Parental history with obesity or diabetes will increase the risk for developing metabolic diseases in offspring. However, literatures as to transgenerational inheritance of metabolic dysfunctions through male lineage are relatively scarce. In the current study, we aimed to evaluate influences of paternal hyperglycemia on metabolic phenotypes in offspring. Male SD rats were i.p. injected with streptozotocin (STZ) or citrate buffer (CB, as control). STZ-injected rats with glucose levels higher than 16.7 mM were selected to breed with normal female rats. Offspring from STZ or CB treated fathers (STZ-O and CB-O) were maintained in the identical condition. We monitored body weight and food intake, and tests of glucose and insulin tolerance (GTTs and ITTs), fasting–refeeding and cold exposure were performed. Expression of factors involved in hypothalamic feeding and brown adipose tissue (BAT) thermogenic activity was performed by real-time PCR and Western blot. Adult STZ-O were heavier than CB-O. Impairment of GTTs was observed in STZ-O compared with CB-O at 22 and 32 weeks of age; ITTs results showed decreased insulin sensitivity in STZ-O. Daily food intake and accumulated food intake during 12-h refeeding after fasting were significantly higher in STZ-O. UCP1 levels were downregulated in BAT from STZ-O at room temperature and cold exposure. Finally, STZ-O rats showed suppressed leptin signaling in the hypothalamus as evidenced by upregulated SOCS3, reduced phosphorylation of STAT3, impaired processing POMC and decreased α-MSH production. Our study revealed that paternal hyperglycemia predisposes offspring to developing obesity, which is possibly associated with impaired hypothalamic leptin signaling.

The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation

2010 ◽  
Vol 298 (6) ◽  
pp. E1244-E1253 ◽  
Author(s):  
G. Barbatelli ◽  
I. Murano ◽  
L. Madsen ◽  
Q. Hao ◽  
M. Jimenez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Cold Acclimatization ◽  
Fat Depots ◽  
Gene Coding ◽  
Adrenoceptor Agonist ◽  
Brown Adipose ◽  
Enhanced Expression

The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT after cold acclimatization have a mixed morphology (paucilocular adipocytes). These cells also had a mixed mitochondrioma with classic “brown” and “white” mitochondria, suggesting intermediate steps in the process of direct transformation of white into brown adipocytes (transdifferentiation). Quantitative electron microscopy disclosed that cold exposure (6°C for 10 days) did not induce an increase in WAT preadipocytes. β3-adrenoceptor-knockout mice had a blunted brown adipocyte occurrence upon cold acclimatization. Administration of the β3-adrenoceptor agonist CL316,243 induced the occurrence of brown adipocytes, with the typical morphological features found after cold acclimatization. In contrast, administration of the β1-adrenoceptor agonist xamoterol increased only the number of preadipocytes. These findings indicate that transdifferentiation depends on β3-adrenoceptor activation, whereas preadipocyte recruitment is mediated by β1-adrenoceptor. RT-qPCR experiments disclosed that cold exposure induced enhanced expression of the thermogenic genes and of genes expressed selectively in brown adipose tissue (iBAT) and in both interscapular BAT and WAT. β3-adrenoceptor suppression blunted their expression only in WAT. Furthermore, cold acclimatization induced an increased WAT expression of the gene coding for C/EBPα (an antimitotic protein), whereas Ccna1 expression (related to cell proliferation) was unchanged. Overall, our data strongly suggest that the cold-induced emergence of brown adipocytes in WAT predominantly reflects β3-adrenoceptor-mediated transdifferentiation.

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