Adaptive Thermogenesis Research Articles

Influence of equation selection on adaptive thermogenesis in obese men: Effects of caloric restriction and probiotic supplementation

Influence of equation selection on adaptive thermogenesis in obese men: Effects of caloric restriction and probiotic supplementation

Slit3 Fragments Orchestrate Neurovascular Expansion and Thermogenesis in Brown Adipose Tissue.

Brown adipose tissue (BAT) represents an evolutionary innovation enabling placental mammals to regulate body temperature through adaptive thermogenesis. Brown adipocytes are surrounded by a dense network of blood vessels and sympathetic nerves that support their development and thermogenic function. Cold exposure stimulates BAT thermogenesis through the coordinated induction of brown adipogenesis, angiogenesis, and sympathetic innervation. However, how these distinct processes are coordinated remains unclear. Here, we identify Slit guidance ligand 3 (Slit3) as a new niche factor that mediates the crosstalk among adipocyte progenitors, endothelial cells, and sympathetic nerves. We show that adipocyte progenitors secrete Slit3 which regulates both angiogenesis and sympathetic innervation in BAT and is essential for BAT thermogenesis in vivo. Proteolytic cleavage of Slit3 generates secreted Slit3-N and Slit3-C fragments, which activate distinct receptors to stimulate angiogenesis and sympathetic innervation, respectively. Moreover, we introduce bone morphogenetic protein-1 (Bmp1) as the first Slit protease identified in vertebrates. In summary, this study underscores the essential role of Slit3-mediated neurovascular network expansion in enabling cold-induced BAT adaptation. The co-regulation of neurovascular expansion by Slit3 fragments provides a bifurcated yet harmonized approach to ensure a synchronized response of BAT to environmental challenges. This study presents the first evidence that adipocyte progenitors regulate tissue innervation, revealing a previously unrecognized dimension of cellular interaction within adipose tissue.

Differential mitochondrial adaptation and FNDC5 production in brown and white adipose tissue in response to cold and obesity.

Fibronectin type III domain-containing protein 5 (FNDC5) modulates adipocyte metabolism by increasing white and brown adipose tissue (WAT and BAT) browning and activity, respectively. We investigated whether FNDC5 can regulate visceral WAT and BAT adaptive thermogenesis by improving mitochondrial homeostasis in response to cold and obesity. Adipose tissue expression of FNDC5 and factors involved in mitochondrial homeostasis were determined in patients with normal weight and obesity (n = 159) and in rats with diet-induced obesity after 1 week of cold exposure (n = 61). The effect of different FNDC5 concentrations on mitochondrial biogenesis, dynamics, and mitophagy was evaluated in vitro in human adipocytes. In human visceral adipocytes, FNDC5/irisin triggered mitochondrial biogenesis (TFAM) and fusion (MFN1, MFN2, and OPA1) while inhibiting peripheral fission (DNM1L and FIS1) and mitophagy (PINK1 and PRKN). Circulating and visceral WAT expression of FNDC5 wasdecreased in patients and experimental animals with obesity, whereas its receptor, integrin αV, was upregulated. Obesity increased mitochondrial fusion while decreasing mitophagy in visceral WAT from patients and rats. By contrast, in rat BAT, an upregulation of Fndc5 and genes involved in mitochondrial biogenesis and fission was observed. Cold exposure promoted mitochondrial biogenesis and healthy peripheral fission while repressing Fndc5 expression and mitophagy in BAT from rats. Depot differences in FNDC5 production and mitochondrial adaptations in response to obesity and cold might indicate a self-regulatory mechanism to control thermogenesis in response to energy needs.

Interaction between adipocytes and macrophages participates in chick subcutaneous adipose tissue angiogenesis under cold stress conditions

Previous studies have shown that subcutaneous adipose tissue is an important energy supply organ for chicks before and after birth, except yolk. So far, the significance of large deposits of subcutaneous adipose tissue in chicks is unclear. Therefore, this study takes the information interaction between adipocytes and macrophages as the starting point to explore whether adipocytes and macrophages could participate in adipose tissue fibrosis, angiogenesis, adaptive thermogenesis and other related functions in a specific metabolic environment. Under cold stress, the expression levels of genes related to lipidolysis, lipid transport and fatty acid oxidation in adipose tissue of chicks were significantly increased, but the expression levels of genes related to mitochondrial uncoupling were not significantly changed. Through Masson staining of adipose tissue of chicks under cold stress, it was found that the level of vascularization in adipose tissue of chicks was significantly increased. We found that the interaction between adipocyte and macrophage could participate in the angiogenesis related process of adipocytes in chicks through the HIF1A–VEGFA pathway. The analysis of lipid metabolism in subcutaneous adipose tissue of chicks from the perspective of cell heterogeneity will expand the understanding of lipid metabolism in chicks and provide a theoretical basis for chick rearing.

Axin interactor, dorsalization-associated (AIDA) protein promotes appetite and regulates hepatic glycolipid metabolism in Schizothorax prenanti

Axin interactor, dorsalization-associated (AIDA) is a protein that interacts with Axin and involved in the regulation of embryonic development, intestinal fat absorption, and adaptive thermogenesis in brown adipose tissue. However, the roles of AIDA in feeding behavior and hepatic glycolipid metabolism in the fish remain uncovered. In this study, the AIDA gene of Schizothorax prenanti (S. prenanti) was cloned and the recombination AIDA protein of S. prenanti was obtained using a prokaryotic expression system. The highest expression level of the AIDA gene was detected in the hypothalamus, followed by the cerebral cortex, liver, muscle, and heart. Fasting induced the expression level of AIDA gene in the liver, cerebral cortex, and hypothalamus, but refeeding attenuated the AIDA expression. Furthermore, the recombinant AIDA protein (200 ng/g BW) i.c.v. injection increased the food intake of S. prenanti by increasing the expression levels of orexigenic factors (AgRP and Ghrelin) and decreasing the expression of anorexigenic factors (Cart, CCK, and Leptin). In addition, the i.p. injection of recombinant AIDA protein significantly decreased the glucose, TC, and TG contents in plasma and reduced the glycogen and TG contents in liver. These results demonstrate that AIDA protein increases appetite and regulates hepatic glycolipid metabolic processes in S. prenanti.

Enrichment of novel CD3+F4/80+ cells in brown adipose tissue following adrenergic stimulation.

Macrophages play a multifaceted role in maintaining tissue homeostasis, fighting infections, and regulating cold-induced thermogenesis. The brown adipose tissue (BAT) is crucial for maintaining body temperature during cold exposure. Cold stress triggers the sympathetic nervous system to release norepinephrine (NE), which activates BAT via β3-adrenergic receptors, initiating lipolysis and glycolysis. BAT-infiltrating macrophages can either hinder or enhance thermogenesis by controlling the interplay between BAT cells and sympathetic nerves. In this study we report on a unique population of CD3+F4/80+ dual lineage co-expressing (DE) cells within the interscapular BAT (iBAT), that increased following chronic adrenergic stimulation. In forward scatter/side scatter plots, they formed a cluster distinct from lymphocytes, appearing larger and more complex. These CD3+F4/80+ DE cells demonstrated the lack of T cell markers CD62L and TCRβ and expressed higher levels of Ly6C, F4/80, and CD11b markers compared to T cells and CD3- macrophages. Furthermore, analysis revealed two subpopulations within the CD3+F4/80+ DE population based on MHCII expression, with the proportion of MHCII-low subset increasing with adrenergic stimulation. This novel DE population within iBAT, unequivocally identified by the its unique surface marker profile, warrants further investigation into the intricate mechanisms governing adaptive thermogenesis regulation.

TRPV1 Activation Antagonizes High-Fat Diet-Induced Obesity at Thermoneutrality and Enhances UCP-1 Transcription via PRDM-16.

Body weight is a balance between energy intake and energy expenditure. Energy expenditure is mainly governed by physical activity and adaptive thermogenesis. Adaptive dietary thermogenesis in brown and beige adipose tissue occurs through mitochondrial uncoupling protein (UCP-1). Laboratory mice, when housed at an ambient temperature of 22-24 °C, maintain their body temperature by dietary thermogenesis, eating more food compared to thermoneutrality. Humans remain in the thermoneutral zone (TNZ) without expending extra energy to maintain normal body temperature. TRPV1 activation by capsaicin (CAP) inhibited weight gain in mice housed at ambient temperature by activating UCP-1-dependent adaptive thermogenesis. Hence, we evaluated the effect of CAP feeding on WT and UCP-1-/- mice maintained under thermoneutral conditions. Our research presents novel findings that TRPV1 activation by CAP at thermoneutrality counters obesity in WT mice and promotes PRDM-16-dependent UCP-1 transcription. CAP fails to inhibit weight gain in UCP-1-/- mice housed at thermoneutrality and in adipose tissue-specific PRDM-16-/- mice. In vitro, capsaicin treatment increases UCP-1 transcription in PRDM-16 overexpressing cells. Our data indicate for the first time that TRPV1 activation counters obesity at thermoneutrality permissive for UCP-1 and the enhancement of PRDM-16 is not beneficial in the absence of UCP-1.

Topical menthol, a pharmacological cold mimic, induces cold sensitivity, adaptive thermogenesis and brown adipose tissue activation in mice.

Brown adipose tissue (BAT) thermogenesis has profound energy-expanding potential, which makes it an attractive target tissue to combat ever-increasing obesity and its other associated metabolic complications. Although it is fairly accepted that cold is a potent inducer of BAT activation and function, there are limited studies on the mechanisms of pharmacological cold-mimicking agents, such as the TRPM8 agonist, menthol, on BAT thermogenesis and activation. Herein, we sought to determine the effect of topical application of menthol (10% w/v [4 g/kg] cream formulation/day for 15 days) on temperature sensitivity behaviour (thermal gradient assay, nesting behaviour), adaptive thermogenesis (infrared thermography, core body temperature), BAT sympathetic innervation (tyrosine hydroxylase immunohistochemistry) and activation (18F-FDG PET-CT analysis, Uncoupling Protein 1 immunohistochemistry and BAT gene expression), whole-body energy expenditure (indirect calorimetry) and other metabolic variables in male C57BL/6N mice. We show that male C57BL/6N mice: (a) develop a warm-seeking and cold-avoiding thermal preference phenotype; (b) display increased locomotor activity and adaptive thermogenesis; (c) show augmented sympathetic innervation in BAT and its activation; (d) exhibit enhanced gluconeogenic capacity (increased glucose excursion in response to pyruvate) and insulin sensitivity; and (e) show enhanced whole-body energy expenditure and induced lipid-utilizing phenotype after topical menthol application. Taken together, our findings highlight that pharmacological cold mimicking using topical menthol application presents a potential therapeutic strategy to counter weight gain and related complications.

Adipose Tissue Dysfunction Related to Climate Change and Air Pollution: Understanding the Metabolic Consequences.

Obesity, a global pandemic, poses a major threat to healthcare systems worldwide. Adipose tissue, the energy-storing organ during excessive energy intake, functions as a thermoregulator, interacting with other tissues to regulate systemic metabolism. Specifically, brown adipose tissue (BAT) is positively associated with an increased resistance to obesity, due to its thermogenic function in the presence of uncoupled protein 1 (UCP1). Recently, studies on climate change and the influence of environmental pollutants on energy homeostasis and obesity have drawn increasing attention. The reciprocal relationship between increasing adiposity and increasing temperatures results in reduced adaptive thermogenesis, decreased physical activity, and increased carbon footprint production. In addition, the impact of climate change makes obese individuals more prone to developing type 2 diabetes mellitus (T2DM). An impaired response to heat stress, compromised vasodilation, and sweating increase the risk of diabetes-related comorbidities. This comprehensive review provides information about the effects of climate change on obesity and adipose tissue, the risk of T2DM development, and insights into the environmental pollutants causing adipose tissue dysfunction and obesity. The effects of altered dietary patterns on adiposity and adaptation strategies to mitigate the detrimental effects of climate change are also discussed.

Integrated analysis of omics reveals the role of scapular fat in thermogenesis adaptation in sunite sheep

Inhabiting some of the world's most inhospitable climatic regions, the Sunite Mongolian sheep generates average temperatures as low as 4.3 °C and a minimum temperature of −38.8 °C; in these environments, they make essential cold adaptations. In this regard, scapular fat tissues from Mongolian sheep were collected both in winter and summer for transcriptomic and proteomic analyses to identify genes related to adaptive thermogenesis. In the transcriptome analysis, 588 differentially expressed genes were identified to participate in smooth muscle activity and fat metabolism, as well as in nutrient regulation. There were 343 upregulated and 245 downregulated genes. GO and KEGG pathway analyses on these genes revealed their participation in regulating smooth muscle activity, metabolism of fats, and nutrients. Proteomic analysis showed the differential expression of 925 proteins: among them, there are 432 up- and 493 down-expressed proteins. These proteins are mainly involved in oxidative phosphorylation, respiratory chain complex assembly, and ATP production by electron transport. Furthermore, using both sets at a more detailed level of analysis revealed over-representation in gene ontology categories related to hormone signaling, metabolism of lipids, the pentose phosphate pathway, the TCA cycle, and especially the process of oxidative phosphorylation. The identified essential genes and proteins were further validated by quantitative real-time polymerase chain reaction and Western blotting, respectively; key metabolic network constriction was constructed. The present study emphasized the critical role of lipid turnover in scapular fat for thermogenic adaptation in Sunite sheep.

Genetic Background Strongly Influences the Impact of Carrying the Thr92Ala-DIO2 Polymorphism in the Male Mouse.

About half of the world population carries at least one allele of the Ala92-DIO2, which slows down the activity of the type 2 deiodinase (D2), the enzyme that activates T4 to T3. Carrying the Ala92-DIO2 allele has been associated with increased body mass index and insulin resistance, but this has not been reproduced in all populations. To test if the genetic background affects the impact of this polymorphism, here we studied the genetically distant C57Bl/6J (B6) and FVB/N (FVB) mice carrying the Ala92-Dio2 allele as compared to control mice carrying the Thr92-Dio2 allele. Whereas B6-Ala92-Dio2 and B6-Thr92-Dio2 mice-fed chow or high-fat diet-behaved metabolically similar in studies using indirect calorimetry, glucose- and insulin tolerance tests, and measuring white adipose tissue (WAT) weight and liver steatosis, major differences were observed between FVB-Ala92-Dio2 and FVB-Thr92-Dio2 mice: carrying the Ala92-Dio2 allele (on a chow diet) resulted in hypercholesterolemia, smaller WAT pads, hepatomegaly, steatosis, and transcriptome changes in the interscapular brown adipose tissue (iBAT) typical of ER stress and apoptosis. Acclimatization at thermoneutrality (30 °C) eliminated most of the metabolic phenotype, indicating that impaired adaptive (BAT) thermogenesis can be involved. In conclusion, the metabolic impact of carrying the Ala92-Dio2 allele depends greatly on the genetic background of the mouse, varying from no phenotype in B6 mice to a major phenotype in FVB mice. These results will help the planning of future clinical trials studying the Thr92Ala-DIO2 polymorphism and may explain why some clinical studies performed in different populations across the globe have obtained inconsistent results.

Regulatory impacts of PPARGC1A gene expression on milk production and cellular metabolism in buffalo mammary epithelial cells

The PPARGC1A gene plays a fundamental role in regulating cellular energy metabolism, including adaptive thermogenesis, mitochondrial biogenesis, adipogenesis, gluconeogenesis, and glucose/fatty acid metabolism. In a previous study, our group investigated seven SNPs in Mediterranean buffalo associated with milk production traits, and the current study builds on this research by exploring the regulatory influences of the PPARGC1A gene in buffalo mammary epithelial cells (BuMECs). Our findings revealed that knockdown of PPARGC1A gene expression significantly affected the growth of BuMECs, including proliferation, cell cycle, and apoptosis. Additionally, we observed downregulated triglyceride secretion after PPARGC1A knockdown. Furthermore, the critical genes related to milk production, including the STATS, BAD, P53, SREBF1, and XDH genes were upregulated after RNAi, while the FABP3 gene, was downregulated. Moreover, Silencing the PPARGC1A gene led to a significant downregulation of β-casein synthesis in BuMECs. Our study provides evidence of the importance of the PPARGC1A gene in regulating cell growth, lipid, and protein metabolism in the buffalo mammary gland. In light of our previous research, the current study underscores the potential of this gene for improving milk production efficiency and overall dairy productivity in buffalo populations.

AGPAT3 deficiency impairs adipocyte differentiation and leads to a lean phenotype in mice.

Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and triglycerides. AGPATs demonstrate unique physiological roles despite a similar biochemical function. AGPAT3 is highly expressed in the testis, kidney, and liver, with intermediate expression in adipose tissue. Loss of AGPAT3 is associated with reproductive abnormalities and visual dysfunction. However, the role of AGPAT3 in adipose tissue and whole body metabolism has not been investigated. We found that male Agpat3 knockout (KO) mice exhibited reduced body weights with decreased white and brown adipose tissue mass. Such changes were less pronounced in the female Agpat3-KO mice. Agpat3-KO mice have reduced plasma insulin growth factor 1 (IGF1) and insulin levels and diminished circulating lipid metabolites. They manifested intact glucose homeostasis and insulin sensitivity despite a lean phenotype. Agpat3-KO mice maintained an energy balance with normal food intake, energy expenditure, and physical activity, except for increased water intake. Their adaptive thermogenesis was also normal despite reduced brown adipose mass and triglyceride content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3-deficient cells. We conclude that AGPAT3 regulates adipogenesis and adipose development. It is possible that adipogenic impairment in Agpat3-deficient cells potentially leads to reduced adipose mass. Findings from this work support the unique role of AGPAT3 in adipose tissue.NEW & NOTEWORTHY AGPAT3 deficiency results in male-specific growth retardation. It reduces adipose tissue mass but does not significantly impact glucose homeostasis or energy balance, except for influencing water intake in mice. Like AGPAT2, AGPAT3 is upregulated during adipogenesis, potentially by peroxisome proliferator-activated receptor gamma (PPARγ). Loss of AGPAT3 impairs adipocyte differentiation, which could be rescued by pioglitazone. Overall, AGPAT3 plays a significant role in regulating adipose tissue mass, partially involving its influence on adipocyte differentiation.

Adipsin and adipocyte-derived C3aR1 regulate thermogenic fat in a sex-dependent fashion.

Thermogenesis in beige/brown adipose tissues can be leveraged to combat metabolic disorders such as type 2 diabetes and obesity. The complement system plays pleiotropic roles in metabolic homeostasis and organismal energy balance with canonical effects on immune cells and noncanonical effects on nonimmune cells. The adipsin/C3a/C3a receptor 1 (C3aR1) pathway stimulates insulin secretion and sustains pancreatic β cell mass. However, its role in adipose thermogenesis has not been defined. Here, we show that male Adipsin/Cfd-knockout mice exhibited increased energy expenditure and white adipose tissue (WAT) browning. In addition, male adipocyte-specific C3aR1-knockout mice exhibited enhanced WAT thermogenesis and increased respiration. In stark contrast, female adipocyte-specific C3aR1-knockout mice displayed decreased brown fat thermogenesis and were cold intolerant. Female mice expressed lower levels of Adipsin in thermogenic adipocytes and adipose tissues than males. C3aR1 was also lower in female subcutaneous adipose tissue than in males. Collectively, these results reveal sexual dimorphism in the adipsin/C3a/C3aR1 axis in regulating adipose thermogenesis and defense against cold stress. Our findings establish a potentially new role of the alternative complement pathway in adaptive thermogenesis and highlight sex-specific considerations in potential therapeutic targets for metabolic diseases.

AGPAT3 deficiency impairs adipocyte differentiation and leads to a lean phenotype in mice

Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and triglycerides. AGPATs demonstrate unique physiological roles despite a similar biochemical function. AGPAT3 is highly expressed in the testis, kidney, and liver, with intermediate expression in adipose tissue. Loss of Agpat3 is associated with reproductive abnormalities and visual dysfunction. However, the role of AGPAT3 in adipose tissue and whole-body metabolism has not been investigated. We found that male Agpat3-KO mice exhibited reduced body weights with decreased white and brown adipose tissue mass. Such changes were less pronounced in the female Agpat3-KO mice. Agpat3-KO mice have reduced plasma insulin growth factor 1 (IGF1) and insulin levels and diminished circulating lipid metabolites. They manifested intact glucose homeostasis and insulin sensitivity despite a lean phenotype. Agpat3-KO mice maintained an energy balance with normal food intake, energy expenditure, and physical activity, except for increased water intake. Their adaptive thermogenesis was also normal despite reduced brown adipose mass and triglyceride content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3 deficient cells. We conclude that AGPAT3 regulates adipogenesis and adipose development. It is possible that adipogenic impairment in Agpat3 deficient cells potentially leads to reduced adipose mass. Findings from this work support the unique role of AGPAT3 in adipose tissue. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases [1R56 DK135657] and the National Heart, Lung and Blood Institute [2R01HL132182-01] to W.C. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Identifying protein domain(s) and interactors necessary for Mcrip2 function in brown adipocytes

High in mitochondria and oxidative capacity, brown adipose tissue (BAT) produces heat through the process of adaptive thermogenesis. Understanding the mechanisms that enable the high oxidative metabolic capacity in BAT can provide insight into and enhance current therapeutic approaches targeting conditions of metabolic dysfunction. Recently, the Kralli lab has identified a gene implicated in BAT thermogenesis that encodes the “mitogen-activated protein kinase (MAPK)-regulated corepressor interacting protein 2” (Mcrip2). Preliminary studies show Mcrip2 regulates the mRNA levels of genes involved in oxidative metabolism, including those involved in oxidative phosphorylation ( Uqcrfs1), fatty acid oxidation ( Acat1, Cpt2), and branched-chain amino acid catabolism ( Bcat2, Bckdha, Ivd, Echs1, Pcca). Interestingly, unbiased proteomic experiments in HEK203 cells have identified multiple Mcrip2 interactors (including Ddx6, Atxn2, Atxn2l) involved in RNA processing, translation and decay, suggesting that this regulation could be post-transcriptional. However, how Mcrip2 post-transcriptionally regulates these genes and the identity of the interactors Mcrip2 constitutes its effects through remains unknown. To elucidate the mechanism of action of Mcrip2, the lab created eight C-terminal HA-tagged Mcrip2 mutant constructs, with mutations targeting different evolutionarily conserved regions of the protein. These mutants will be expressed in primary brown adipocytes lacking Mcrip2 to determine if they complement wild-type and will also be used for co-immunoprecipitation. Results from such studies may provide further insight into the role of Mcrip2 in adipocyte oxidative metabolism and, more broadly, in BAT function. NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Smooth muscle cell-derived Cxcl12 directs macrophage accrual and sympathetic innervation to control thermogenic adipose tissue

Sympathetic innervation of brown adipose tissue (BAT) controls mammalian adaptative thermogenesis. However, the cellular and molecular underpinnings contributing to BAT innervation remain poorly defined. Here, we show that smooth muscle cells (SMCs) support BAT growth, lipid utilization, and thermogenic plasticity. Moreover, we find that BAT SMCs express and control the bioavailability of Cxcl12. SMC deletion of Cxcl12 fosters brown adipocyte lipid accumulation, reduces energy expenditure, and increases susceptibility to diet-induced metabolic dysfunction. Mechanistically, we find that Cxcl12 stimulates CD301+ macrophage recruitment and supports sympathetic neuronal maintenance. Administering recombinant Cxcl12 to obese mice or leptin-deficient (Ob/Ob) mice is sufficient to boost macrophage presence and drive sympathetic innervation to restore BAT morphology and thermogenic responses. Altogether, our data reveal an SMC chemokine-dependent pathway linking immunological infiltration and sympathetic innervation as a rheostat for BAT maintenance and thermogenesis.

Adaptive thermogenesis, at the level of resting energy expenditure, after diet alone or diet plus bariatric surgery.

The objective of this study was to compare the magnitude of adaptive thermogenesis (AT), at the level of resting energy expenditure (REE), after a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy, as well as to investigate the association between AT and changes in appetite. A total of 44 participants with severe obesity underwent 10 weeks of a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy. Body weight and composition, REE, subjective appetite feelings, and plasma concentrations of gastrointestinal hormones were measured at baseline and week 11. AT, at the level of REE, was defined as a significantly lower measured versus predicted (using a regression model with baseline data) REE. Participants lost 18.4 ± 3.9 kg of body weight and experienced AT, at the level of REE (-121 ± 188 kcal/day; p < 0.001), with no differences among groups. The larger the AT, at the level of REE, the greater the reduction in fasting ghrelin concentrations and the smaller the reduction in feelings of hunger and desire to eat in the postprandial state. Weight-loss modality does not seem to modulate the magnitude of AT, at the level of REE. The greater the AT, at the level of REE, the greater the drive to eat following weight loss.

Adaptive thermogenesis of the brown adipose tissue in Apodemus chevrieri during cold acclimation

Abstract To investigate the effect of low temperature on body mass, thermogenic activity, and Uncoupling protein-1 (UCP1) content of brown adipose tissue (BAT) in Chevrier’s field mouse (Apodemus chevrieri), 50 healthy adult mice with similar body mass were used in our experiment. They were divided into five groups of ten individuals as follows: a control group (0 d), where animals were maintained under 25 ± 1°C and a 12L:12D (light:dark, lights on 08:00) photoperiod; the other groups were maintained under 5 ± 1°C and a 12L:12D photoperiod for 7 d, 14 d, 21 d and 28 d, respectively. At the end of the experiment, the changes in body mass, resting metabolic rate (RMR), nonshivering thermogenesis (NST), BAT mass, mitochondrial protein (MP) content, cytochrome c oxidase (COX) activity, and UCP1 content were measured. The results showed that compared with the control group (0 d), the body mass of the cold acclimation groups decreased significantly. In contrast, RMR, NST, BAT mass, MP content, COX activity, and UCP1 content of the cold acclimation group increased significantly. After cold acclimation for 28 days, RMR increased by 89.4%, NST increased by 50.4%, BAT mass increased by 44.6%, and UCP1 content increased by 36.0%. The ratio of (NST − RMR)/RMR was 1.03 after seven days and then dropped to 0.59 on day 21, and remained at a steady level thereafter. Evidently, NST was significantly positively correlated with BAT mass and UCP1 content. The results indicated that under continuous cold exposure, A. chevrieri could take appropriate measures to reduce body mass, increase RMR, induce BAT tissue proliferation, and unregulated UCP1 expression, thereby enhancing BAT thermogenic activity to cope with a low-temperature environment. In the early stage of cold acclimation, NST was dominant in thermogenesis, but as time continued, it reduced. This may represent a unique energy adaptation strategy of small rodents originating from the north and spreading southward toward the Hengduan Mountain regions.

Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF

Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.