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1.
J Ethnopharmacol ; 302(Pt A): 115700, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36126782

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a critical threat to global health, and brown adipose tissue (BAT) is a potential target for the treatment of obesity and comorbidities. Xuezhikang Capsule (XZK), an extract of red yeast rice, has remarkable clinical efficacy and is widely used for the treatment of hyperlipidemia and coronary heart disease. However, its modulatory effect on BAT remains unknown. AIM OF THIS STUDY: The aim of this study was to investigate the protective mechanism of XZK in the obese spontaneously hypertensive rat (SHR) model by evaluating the regulatory effect of XZK on the BAT gene profile through transcriptome sequencing. MATERIALS AND METHODS: The SHRs were randomly divided into four groups: the standard chow diet (STD) group, the STD supplemented with 126 mg/kg of XZK group, the high-fat diet (HFD) group, and the HFD supplemented with 126 mg/kg of XZK group. All SHRs were fed for 18 weeks. The metabolic phenotypes, including body weight, fat mass, oral glucose tolerance test (OGTT), and serum glucose and lipid levels, was evaluated, and hematoxylin and eosin staining (H&E) staining was performed to evaluate the adipose tissue histopathological phenotype. Transcriptome sequencing was performed to determine the mechanism by which XZK improves the metabolic phenotype and the expression of key differential expression genes was verified by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: XZK inhibited HFD-induced weight gain and adipose tissue remodeling in SHRs and prevented hypertrophy of epididymal adipocytes and maintained the brown fat phenotype. XZK intervention also improved glucose and lipid metabolism in SHRs, as suggested by a reduction in serum triglyceride (TG), low-density cholesterol (LDL-C), and fasting blood glucose (FBG) levels as well as increasing in serum high-density cholesterol (HDL-C) levels. Transcriptome sequencing analysis confirmed the regulatory effect of XZK on the gene expression profile of BAT, and the expression patterns of 45 genes were reversed by the XZK intervention. Additionally, the results of the transcriptome analysis of 10 genes that are important for brown fat function were in line with the results of qRT-PCR. CONCLUSIONS: XZK protected SHRs from HFD-induced obesity, inhibited fat accumulation and improved glucolipid metabolism. Additionally, the protective effect of XZK on the overall metabolism of obese SHRs might partly be related to its regulatory effect on the BAT gene expression profile. These findings might provide novel therapeutic strategies for obesity-related metabolic diseases in traditional Chinese medicine (TCM).


Assuntos
Hiperlipidemias , Doenças Metabólicas , Infecções Sexualmente Transmissíveis , Ratos , Animais , Camundongos , Tecido Adiposo Marrom/metabolismo , Ratos Endogâmicos SHR , Transcriptoma , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Dieta Hiperlipídica , Tecido Adiposo/metabolismo , Colesterol , Glucose , Camundongos Endogâmicos C57BL
2.
J Nutr Biochem ; 111: 109160, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36179768

RESUMO

Mammals maintain constant body temperature in cold environment by activating thermogenesis via adrenergic/protein kinase A (PKA) signaling. B-cell translocation gene 2 (BTG2/Tis21), induced by PKA signaling, regulates glucose and lipid metabolism in liver, yet its role in lipolysis and in thermogenesis is not explored. Here, Btg2-knockout (KO) mice failed to maintain body temperature under starvation, or in cold acclimation. And norepinephrine-induced thermogenic response was turned off earlier in the KO mice. Gender specifically, gonadal white adipose tissues (gWAT) of female-KO were very active in lipolysis in fed state, however, the fat degradation was diminished upon fasting or cold acclimation. Also, insulin sensitivity was increased in female-KO, but not in male-KO mice, along with the low bone mineral density and small brown adipose tissues (BAT). In the mechanistic aspect, expressions of UCP1 and lipases (LPL, ATGL, HSL) in gWAT of female-KO mice were significantly reduced in response to adrenergic signals. Here, we present some data that Btg2 gene is essential for properly respond to ß-adrenergic signals, and plays as a negative regulator of insulin signaling in female mice.


Assuntos
Proteínas Imediatamente Precoces , Lipólise , Termogênese , Animais , Feminino , Masculino , Camundongos , Aclimatação , Tecido Adiposo Marrom/metabolismo , Temperatura Baixa , Lipólise/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo
3.
Obesity (Silver Spring) ; 30(11): 2242-2255, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36321273

RESUMO

OBJECTIVE: Elevation of energy expenditure through an increase of brown adipose tissue (BAT) thermogenesis is regarded as one of the most promising ways to prevent obesity development. The preoptic area (POA) of the hypothalamus is a critical area for control of BAT thermogenesis. However, the intracellular signaling cascades in the POA for regulation of BAT thermogenesis are poorly understood. METHODS: Phosphorylation proteomics (phosphoproteomics) and bioinformatics approaches were used to disclose numerous hypothalamic signaling pathways involved in the regulation of BAT thermogenesis. Conditional manipulation of the p38α gene in mouse POA was performed by stereotaxic injection of adeno-associated virus 9 vector to explore the role of p38α in BAT thermogenesis. RESULTS: Multiple hypothalamic signaling pathways were triggered by cold exposure, especially the mitogen-activated protein kinase (MAPK) signaling pathway. The p38α activation, but not extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK), in the hypothalamus was significantly decreased during cold exposure. p38α deficiency in the POA dramatically elevated energy expenditure owing to a marked increase in BAT thermogenesis, resulting in significantly decreased body weight gain and fat mass. Overexpression of p38α in the POA led to a dramatic increase in weight gain. CONCLUSIONS: These results demonstrate that p38α in the POA exacerbates obesity development, at least in part owing to a decrease in BAT thermogenesis.


Assuntos
Tecido Adiposo Marrom , Área Pré-Óptica , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Área Pré-Óptica/metabolismo , Termogênese/fisiologia , Obesidade/metabolismo , Metabolismo Energético/fisiologia , Aumento de Peso
4.
Sci Rep ; 12(1): 18753, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335116

RESUMO

The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via 18F-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (- 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (- 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (ß: 0.44, 95% CI [0.06-0.81], P = 0.024) after adjusting for study design but not BAT volume (ß: 0.39, 95% CI [- 0.01-0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.


Assuntos
Tecido Adiposo Marrom , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Humanos , Tecido Adiposo Marrom/metabolismo , Apolipoproteínas M/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/metabolismo
5.
Nat Commun ; 13(1): 7303, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435799

RESUMO

White adipose tissue browning is a key metabolic process controlled by epigenetic factors that facilitate changes in gene expression leading to altered cell identity. We find that male mice lacking the nucleosome binding proteins HMGN1 and HMGN2 (DKO mice), show decreased body weight and inguinal WAT mass, but elevated food intake, WAT browning and energy expenditure. DKO white preadipocytes show reduced chromatin accessibility and lower FRA2 and JUN binding at Pparγ and Pparα promoters. White preadipocytes and mouse embryonic fibroblasts from DKO mice show enhanced rate of differentiation into brown-like adipocytes. Differentiating DKO adipocytes show reduced H3K27ac levels at white adipocyte-specific enhancers but elevated H3K27ac levels at brown adipocyte-specific enhancers, suggesting a faster rate of change in cell identity, from white to brown-like adipocytes. Thus, HMGN proteins function as epigenetic factors that stabilize white adipocyte cell identity, thereby modulating the rate of white adipose tissue browning and affecting energy metabolism in mice.


Assuntos
Tecido Adiposo Marrom , Nucleossomos , Masculino , Animais , Camundongos , Nucleossomos/metabolismo , Tecido Adiposo Marrom/metabolismo , Proteínas HMGN/metabolismo , Epigênese Genética , Fibroblastos/metabolismo , Tecido Adiposo Branco/metabolismo , Adipócitos Marrons/metabolismo , Metabolismo Energético/genética
6.
Yi Chuan ; 44(10): 867-880, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384724

RESUMO

The activation of brown adipose tissues and beige adipose tissues can utilize more substrates, including glucose and fatty acids, regulate the energy balance of the whole body and improve metabolic diseases such as obesity and type Ⅱ diabetes. Elucidating the regulatory mechanisms underlying the thermogenic adipose program may provide excellent targets for therapeutics against metabolic diseases. The current studies have indicated that epigenetic modifications are vital for regulating differentiation and thermogenesis of adipose tissues. In this review, we summarize the recent progress of epigenetic modifications in adipose tissue development and thermogenesis from the aspects of DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs in order to provide new ideas for further studying the activation of adipose tissues.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Humanos , Epigênese Genética , Termogênese/genética , Tecido Adiposo Marrom/metabolismo , Doenças Metabólicas/metabolismo
7.
Int J Mol Sci ; 23(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36361843

RESUMO

Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to promote white adipocyte differentiation, its role in BAT remains unclear. In our study, we found that during HFD-induced obesity, the expression of miR-143 in BAT was significantly reduced, and the expression of miR-143 in WAT first increased and then decreased. Knockout (KO) of miR-143 with CRISPR/Cas9 did not affect the energy metabolism of normal diet fed mice and brown adipocyte differentiation but inhibited the differentiation of white adipocytes. Importantly, during high fat diet-induced obesity, miR-143KO significantly reduced body weight, and improved energy expenditure, insulin sensitivity, and glucose tolerance. Further exploration showed that miR-143KO reduced the weight of adipose tissue, promoted mitochondrial number and functions, induced thermogenesis and lipolysis of BAT, increased lipolysis, and inhibited lipogenesis of white adipose tissue (WAT). Our study considerably improves our collective understanding of the function of miR-143 in adipose tissue and its potential significance in anti-obesity and provides a new avenue for the management of obesity through the inhibition of miR-143 in BAT and WAT.


Assuntos
Tecido Adiposo Marrom , MicroRNAs , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Adipogenia/genética , Camundongos Knockout , Termogênese/genética , Tecido Adiposo Branco/metabolismo , Obesidade/genética , Obesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos Endogâmicos C57BL
8.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36361929

RESUMO

Brown adipose tissue (BAT) has been widely studied in targeting against metabolic diseases such as obesity, type 2 diabetes and insulin resistance due to its role in nutrient metabolism and energy regulation. Whether exercise promotes adipose tissue thermogenesis and browning remains controversial. The results from human and rodent studies contradict each other. In our opinion, fat thermogenesis or browning promoted by exercise should not be a biomarker of health benefits, but an adaptation under the stress between body temperature regulation and energy supply and expenditure of multiple organs. In this review, we discuss some factors that may contribute to conflicting experimental results, such as different thermoneutral zones, gender, training experience and the heterogeneity of fat depots. In addition, we explain that a redox state in cells potentially causes thermogenesis heterogeneity and different oxidation states of UCP1, which has led to the discrepancies noted in previous studies. We describe a network by which exercise orchestrates the browning and thermogenesis of adipose tissue with total energy expenditure through multiple organs (muscle, brain, liver and adipose tissue) and multiple pathways (nerve, endocrine and metabolic products), providing a possible interpretation for the conflicting findings.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Termogênese , Tecido Adiposo Marrom/metabolismo , Obesidade/metabolismo , Aclimatação , Tecido Adiposo Branco/metabolismo , Metabolismo Energético
9.
Nat Metab ; 4(11): 1573-1590, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36400933

RESUMO

Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)-nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis.


Assuntos
Tecido Adiposo Marrom , Aterosclerose , Neurregulinas , Animais , Masculino , Camundongos , Tecido Adiposo Marrom/metabolismo , Aterosclerose/metabolismo , Células Endoteliais/metabolismo , Endotélio , Inflamação/metabolismo , Neurregulinas/metabolismo
10.
Clin Nucl Med ; 47(12): 1112-1113, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36342799

RESUMO

ABSTRACT: Characterization of brown adipose tissue (BAT) 18F-FDG uptake has been well reported; however, 68Ga-DOTA-conjugated somatostatin receptor targeting peptides uptake in BAT is rarely documented. Herein, we report an interesting case of increased 68Ga-DOTATATE uptake in supraclavicular BAT in a young boy with paroxysmal hypertension. The low body mass index and increased perfusion of BAT in response to cold may be significant influencing factors.


Assuntos
Tecido Adiposo Marrom , Fluordesoxiglucose F18 , Masculino , Humanos , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Fluordesoxiglucose F18/metabolismo , Transporte Biológico
11.
Neuron ; 110(21): 3597-3626, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36327900

RESUMO

The sympathetic nervous system maintains metabolic homeostasis by orchestrating the activity of organs such as the pancreas, liver, and white and brown adipose tissues. From the first renderings by Thomas Willis to contemporary techniques for visualization, tracing, and functional probing of axonal arborizations within organs, our understanding of the sympathetic nervous system has started to grow beyond classical models. In the present review, we outline the evolution of these findings and provide updated neuroanatomical maps of sympathetic innervation. We offer an autonomic framework for the neuroendocrine loop of leptin action, and we discuss the role of immune cells in regulating sympathetic terminals and metabolism. We highlight potential anti-obesity therapeutic approaches that emerge from the modern appreciation of SNS as a neural network vis a vis the historical fear of sympathomimetic pharmacology, while shifting focus from post- to pre-synaptic targeting. Finally, we critically appraise the field and where it needs to go.


Assuntos
Neuroimunomodulação , Sistema Nervoso Simpático , Humanos , Sistema Nervoso Simpático/metabolismo , Obesidade , Tecido Adiposo Marrom/metabolismo , Homeostase
12.
Nutrients ; 14(21)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36364955

RESUMO

"Ferrocrinology" is the term used to describe the study of iron effects on the functioning of adipose tissue, which together with muscle tissue makes the largest endocrine organ in the human body. By impairing exercise capacity, reducing AMP-activated kinase activity, and enhancing insulin resistance, iron deficiency can lead to the development of obesity and type 2 diabetes mellitus. Due to impaired browning of white adipose tissue and reduced mitochondrial iron content in adipocytes, iron deficiency (ID) can cause dysfunction of brown adipose tissue. By reducing ketogenesis, aconitase activity, and total mitochondrial capacity, ID impairs muscle performance. Another important aspect is the effect of ID on the impairment of thermogenesis due to reduced binding of thyroid hormones to their nuclear receptors, with subsequently impaired utilization of norepinephrine in tissues, and impaired synthesis and distribution of cortisol, which all make the body's reactivity to stress in ID more pronounced. Iron deficiency can lead to the development of the most common endocrinopathy, autoimmune thyroid disease. In this paper, we have discussed the role of iron in the cross-talk between glucocrinology, lipocrinology and myocrinology, with thyroid hormones acting as an active bystander.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Ferro/metabolismo , Tecido Adiposo Marrom/metabolismo , Termogênese , Tecido Adiposo Branco/metabolismo , Hormônios Tireóideos/metabolismo , Metabolismo Energético/fisiologia
13.
Cell ; 185(24): 4654-4673.e28, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36334589

RESUMO

Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited the understanding of generalizable mechanisms of BAT regulation over physiology. Here, we perform deep quantitative proteomics of BAT across a cohort of 163 genetically defined diversity outbred mice, a model that parallels the genetic and phenotypic variation found in humans. We leverage this diversity to define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functions to 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify 638 proteins that correlate with protection from, or sensitivity to, at least one parameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, and ATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resource for understanding the conserved mechanisms of BAT regulation over metabolic physiology.


Assuntos
Tecido Adiposo Marrom , Proteoma , Humanos , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Proteoma/metabolismo , Termogênese/fisiologia , Adiposidade , Obesidade/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas/metabolismo
14.
Elife ; 112022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36374165

RESUMO

Thyroid hormone (T3) and its nuclear receptors (TR) are important regulators of energy expenditure and adaptive thermogenesis, notably through their action in the brown adipose tissue (BAT). However, T3 acts in many other peripheral and central tissues which are also involved in energy expenditure. The general picture of how T3 regulates BAT thermogenesis is currently not fully established, notably due to the absence of extensive omics analyses and the lack of specific mice model. Here, we first used transcriptome and cistrome analyses to establish the list of T3/TR direct target genes in brown adipocytes. We then developed a novel model of transgenic mice, in which T3 signaling is specifically suppressed in brown adipocytes at adult stage. We addressed the capacity of these mice to mount a thermogenic response when challenged by either a cold exposure or a high-fat diet, and analyzed the associated changes in BAT transcriptome. We conclude that T3 plays a crucial role in the thermogenic response of the BAT, controlling the expression of genes involved in lipid and glucose metabolism and regulating BAT proliferation. The resulting picture provides an unprecedented view on the pathways by which T3 activates energy expenditure through an efficient adaptive thermogenesis in the BAT.


Assuntos
Adipócitos Marrons , Termogênese , Camundongos , Masculino , Animais , Adipócitos Marrons/metabolismo , Termogênese/fisiologia , Tecido Adiposo Marrom/metabolismo , Hormônios Tireóideos/metabolismo , Metabolismo Energético , Camundongos Transgênicos , Camundongos Endogâmicos C57BL
15.
Nat Commun ; 13(1): 7269, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36433953

RESUMO

While the endocrine function of white adipose tissue has been extensively explored, comparatively little is known about the secretory activity of less-investigated fat depots. Here, we use proteomics to compare the secretory profiles of male murine perivascular depots with those of canonical white and brown fat. Perivascular secretomes show enrichment for neuronal cell-adhesion molecules, reflecting a higher content of intra-parenchymal sympathetic projections compared to other adipose depots. The sympathetic innervation is reduced in the perivascular fat of obese (ob/ob) male mice, as well as in the epicardial fat of patients with obesity. Degeneration of sympathetic neurites is observed in presence of conditioned media of fat explants from ob/ob mice, that show reduced secretion of neuronal growth regulator 1. Supplementation of neuronal growth regulator 1 reverses this neurodegenerative effect, unveiling a neurotrophic role for this protein previously identified as a locus associated with human obesity. As sympathetic stimulation triggers energy-consuming processes in adipose tissue, an impaired adipose-neuronal crosstalk is likely to contribute to the disrupted metabolic homeostasis characterising obesity.


Assuntos
Tecido Adiposo Marrom , Obesidade , Humanos , Masculino , Camundongos , Animais , Camundongos Obesos , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo
16.
Int J Mol Sci ; 23(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36293005

RESUMO

Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli-such as exercise, cold exposure, and drug treatment-white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the 'browning of WAT'. We evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity.


Assuntos
Adipócitos Brancos , Células-Tronco Mesenquimais , Animais , Adipócitos Brancos/metabolismo , Fibronectinas/metabolismo , Rosiglitazona/farmacologia , Citrato de Sildenafila/farmacologia , Medula Óssea/metabolismo , Metabolismo Energético , Termogênese , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Células-Tronco Mesenquimais/metabolismo , Glucose/metabolismo , Triglicerídeos/metabolismo , Mamíferos/metabolismo
17.
Nutr Diabetes ; 12(1): 42, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207302

RESUMO

BACKGROUNDS/OBJECTIVES: Melatonin promotes brown adipose tissue (BAT) activity, leading to body mass reduction and energy expenditure. However, the mechanisms governing these beneficial effects are not well-established. This study aimed to assess the effects of (1) melatonin on BAT and energy metabolism, and (2) fibroblast growth factor 21 (FGF21) in BAT-mediated thermogenesis. METHODS: Male C57BL/6 J mice received a high-fat diet (HFD) or normal chow, accompanied by intraperitoneal injection of 20 mg/kg melatonin for 12 weeks. FGF21-/- mice consumed an HFD with or without melatonin for 8 weeks. RESULTS: Melatonin attenuated weight gain, insulin resistance, adipocyte hypertrophy, inflammation, and hepatic steatosis induced by the HFD and increased energy expenditure. Furthermore, melatonin improved cold tolerance by increasing BAT uncoupling protein 1 (UCP1) expression and producing heat. Notably, melatonin resulted in a shift in energy metabolism favouring the utilization of fat, and it increased FGF21 in circulating and metabolic tissues and skeletal muscle phosphorylation of AMP-activated protein kinase. However, melatonin did not protect against obesity, insulin resistance, and energy expenditure in HFD-fed FGF21-/- mice. CONCLUSIONS: Melatonin suppressed obesity and insulin resistance resulting from the HFD by enhancing BAT activity and energy expenditure, and these effects were dependent on FGF21.


Assuntos
Resistência à Insulina , Melatonina , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica , Metabolismo Energético/fisiologia , Lipólise , Masculino , Melatonina/metabolismo , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Proteína Desacopladora 1/metabolismo
18.
Int J Mol Sci ; 23(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36233205

RESUMO

The role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of energy homeostasis remains poorly understood. In this study, we used a transgenic fat-1 mouse model, which can produce n-3 PUFAs endogenously, to investigate how n-3 PUFAs regulate the morphology and function of brown adipose tissue (BAT). We found that high-fat diet (HFD) induced a remarkable morphological change in BAT, characterized by "whitening" due to large lipid droplet accumulation within BAT cells, associated with obesity in wild-type (WT) mice, whereas the changes in body fat mass and BAT morphology were significantly alleviated in fat-1 mice. The expression of thermogenic markers and lypolytic enzymes was significantly higher in fat-1 mice than that in WT mice fed with HFD. In addition, fat-1 mice had significantly lower levels of inflammatory markers in BAT and lipopolysaccharide (LPS) in plasma compared with WT mice. Furthermore, fat-1 mice were resistant to LPS-induced suppression of UCP1 and PGC-1 expression and lipid deposits in BAT. Our data has demonstrated that high-fat diet-induced obesity is associated with impairments of BAT morphology (whitening) and function, which can be ameliorated by elevated tissue status of n-3 PUFAs, possibly through suppressing the effects of LPS on inflammation and thermogenesis.


Assuntos
Tecido Adiposo Marrom , Ácidos Graxos Ômega-3 , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Termogênese
19.
J Agric Food Chem ; 70(43): 13893-13903, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36264038

RESUMO

The antiobesity efficacy and underlying mechanisms of polysaccharides extracted from Fu brick tea (FBTP) were investigated. An 8-week administration of FBTP dose-dependently inhibited increases in body weight and weights of the epididymal-, retroperitoneal- and inguinal-white adipose tissues and stimulated beige-fat development and brown adipose tissue-derived nonshivering thermogenesis in high-fat diet-induced obese mice. FBTP protected against obesity-associated abnormality in serum adiponectin and leptin, indicating its positive regulation of energy metabolism. FBTP reversed gut dysbiosis by enriching beneficial bacteria, for example, Lactobacillus, Parabacteroides, Akkermansia, Bifidobacterium, and Roseburia. Results from the fecal microbiota transplantation further confirmed that FBTP-induced microbial shifts contributed to adipose browning and thermogenesis, thereby alleviating host adiposity, glucose homeostasis, dyslipidemia, and its related hepatic steatosis. Our study demonstrates the great potential of FBTP with prebiotic-like activities in preventing diet-induced obesity and its related metabolic complications via gut microbiota-derived enhancement of fat burning and energy expenditures.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Chá/metabolismo , Termogênese , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica , Camundongos Obesos , Adipócitos/metabolismo , Polissacarídeos/metabolismo , Camundongos Endogâmicos C57BL
20.
Mol Cells ; 45(10): 673-684, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36254709

RESUMO

The past two decades have witnessed an upsurge in the appreciation of adipose tissue (AT) as an immuno-metabolic hub harbouring heterogeneous cell populations that collectively fine-tune systemic metabolic homeostasis. Technological advancements, especially single-cell transcriptomics, have offered an unprecedented opportunity for dissecting the sophisticated cellular networks and compositional dynamics underpinning AT remodelling. The "re-discovery" of functional brown adipose tissue dissipating heat energy in human adults has aroused tremendous interest in exploiting the mechanisms underpinning the engagement of AT thermogenesis for combating human obesity. In this review, we aim to summarise and evaluate the use of single-cell transcriptomics that contribute to a better appreciation of the cellular plasticity and intercellular crosstalk in thermogenic AT.


Assuntos
Tecido Adiposo , Metabolismo Energético , Termogênese , Adulto , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo Marrom/metabolismo , Homeostase , Obesidade/metabolismo
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