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BackgroundPerivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways.MethodsSprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed.ResultsChronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT.ConclusionRegular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.

Introduction: The energy imbalance when energy intake exceeds expenditure acts as an essential factor in the development of insulin resistance (IR). The activity of brown adipose tissue, which is involved in the dissipation of energy via heat expenditure decreases under type 2 diabetic mellitus (T2DM) state when the number of pathological aging adipocytes increases. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates several biological processes by dephosphorylating several cellular substrates; however, whether PTPN2 regulates cellular senescence in adipocytes and the underlying mechanism has not been reported. Methods: We constructed a model of type 2 diabetic mice with PTPN2 overexpression to explore the role of PTPN2 in T2DM. Results: We revealed that PTPN2 facilitated adipose tissue browning by alleviating pathological senescence, thus improving glucose tolerance and IR in T2DM. Mechanistically, we are the first to report that PTPN2 could bind with transforming growth factor-activated kinase 1 (TAK1) directly for dephosphorylation to inhibit the downstream MAPK/NF-κB pathway in adipocytes and regulate cellular senescence and the browning process subsequently. Discussion: Our study revealed a critical mechanism of adipocytes browning progression and provided a potential target for the treatment of related diseases. [ABSTRACT FROM AUTHOR]

Mulberry leaf is an important medicinal food plant, which is rich in polyphenol compounds. Mulberry leaf polyphenols (MLP) possess significant lipid-lowering and antioxidant effects, and healthcare functions. In this study, the polyphenol content of mulberry leaf ethanol extract was measured using HPLC. The analysis of mulberry leaf extract resulted in the identification of 14 compounds, of which Chlorogenic acid and Quercitrin were the highest. A high-fat diet (HFD)-induced obese mouse model was developed and treated with MLP for 12 weeks to explore their effect on lipid metabolism in HFD-induced obese mice. The results showed that the MLP could inhibit the weight gain and fat cell volume increase in the HFD-induced obese mice in a dose-dependent manner. Further analysis revealed that the MLP decelerated the fatty acid composition in the adipose tissues of HFD-induced obese mice, and significantly increased the polyunsaturated-to-saturated fatty acid (PUFA/SFA) ratio. The real-time quantitative PCR (RT-qPCR) results indicated that the MLP significantly inhibited the down regulation of uncoupling protein (UCP) 1 (UCP1), UCP3, and PR domain zinc finger protein 16 (PRDM16) caused by the HFD. These beneficial effects of MLP on HFD-induced obese mice might be attributed to their ability to change the fatty acid composition of adipose tissue and increase the expression of thermogenesis genes. Overall, the study results suggested that the MLP could serve as potential lipid-lowering and weight-loss functional food and healthcare products.

Cancer cachexia is a disorder of energy balance characterized by the wasting of adipose tissue and skeletal muscle resulting in severe weight loss with profound influence on morbidity and mortality. Treatment options for cancer cachexia are still limited. This multifactorial syndrome is associated with changes in several metabolic pathways in adipose tissue which is affected early in the course of cachexia. Adipose depots are involved in energy storage and consumption as well as endocrine functions. In this mini review, we discuss the metabolic reprogramming in all three types of adipose tissues – white, brown, and beige – under the influence of the tumor macro-environment. Alterations in adipose tissue lipolysis, lipogenesis, inflammation and adaptive thermogenesis of beige/brown adipocytes are highlighted. Energy-wasting circuits in adipose tissue impacts whole-body metabolism and particularly skeletal muscle. Targeting of key molecular players involved in the metabolic reprogramming may aid in the development of new treatment strategies for cancer cachexia. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a disorder of energy balance characterized by the wasting of adipose tissue and skeletal muscle resulting in severe weight loss with profound influence on morbidity and mortality. Treatment options for cancer cachexia are still limited. This multifactorial syndrome is associated with changes in several metabolic pathways in adipose tissue which is affected early in the course of cachexia. Adipose depots are involved in energy storage and consumption as well as endocrine functions. In this mini review, we discuss the metabolic reprogramming in all three types of adipose tissues – white, brown, and beige – under the influence of the tumor macro-environment. Alterations in adipose tissue lipolysis, lipogenesis, inflammation and adaptive thermogenesis of beige/brown adipocytes are highlighted. Energy-wasting circuits in adipose tissue impacts whole-body metabolism and particularly skeletal muscle. Targeting of key molecular players involved in the metabolic reprogramming may aid in the development of new treatment strategies for cancer cachexia.

Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

In recent years, brown adipose tissue (BAT) has gained significance as a metabolic organ dissipating energy through heat production. Promotion of a thermogenic program in fat holds great promise as potential therapeutic tool to counteract weight gain and related sequelae. Current research efforts are aimed at identifying novel pathways regulating brown fat function and the transformation of white adipocytes into BAT-like cells, a process called “browning.” Besides numerous genetic factors some circulating molecules can act as mediators of adipose tissue thermogenesis. Vitamin A metabolites, the retinoids, are potent regulators of gene transcription through nuclear receptor signaling and are thus involved in a plethora of metabolic processes. Accumulating evidence links retinoid action to brown fat function and browning of WAT mainly via orchestrating a transcriptional BAT program in adipocytes including expression of key thermogenic genes such as uncoupling protein 1. Here we summarize the current understanding how retinoids play a role in adipose tissue thermogenesis through transcriptional control of thermogenic gene cassettes and potential non-genomic mechanisms.

In recent years, brown adipose tissue (BAT) has gained significance as a metabolic organ dissipating energy through heat production. Promotion of a thermogenic program in fat holds great promise as potential therapeutic tool to counteract weight gain and related sequelae. Current research efforts are aimed at identifying novel pathways regulating brown fat function and the transformation of white adipocytes into BAT-like cells, a process called "browning." Besides numerous genetic factors some circulating molecules can act as mediators of adipose tissue thermogenesis. Vitamin A metabolites, the retinoids, are potent regulators of gene transcription through nuclear receptor signaling and are thus involved in a plethora of metabolic processes. Accumulating evidence links retinoid action to brown fat function and browning of WAT mainly via orchestrating a transcriptional BAT program in adipocytes including expression of key thermogenic genes such as uncoupling protein 1. Here we summarize the current understanding how retinoids play a role in adipose tissue thermogenesis through transcriptional control of thermogenic gene cassettes and potential non-genomic mechanisms. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the influence of electroacupuncture (EA) and its potential underlying mechanisms on adipose tissue in obese mice.Methods: Three-week-old male C56BL/6 mice were randomly divided to feed or not to feed high-fat diet (HFD), named HFD group and chow diet (CD) group, respectively. After 12 weeks, CD and HFD mice were randomly divided into two groups, respectively, to receive or not receive EA for 4 weeks. Body weight (BW) was monitored. Intraperitoneal glucose tolerance test and metabolic chamber recordings were performed. Blood samples and adipose tissue were collected for the analysis of leptin, triglyceride levels, and fat browning-related proteins.Results: EA significantly reduced food intake, BW, and white adipose tissue (WAT)/BW ratio; decreased the adipocyte size and serum concentrations of triglyceride (TG) and cholesterol; and increased oxygen consumption in HFD mice. Compared with the CD mice, the HFD mice had elevated fasting serum glucose level and impaired glucose tolerance; however, these parameters were decreased by EA treatment. Meanwhile, EA promoted the protein and mRNA expressions of UCP1, PRDM16, and PGC-1α in adipose tissue, and activated sympathetic nerves via p-TH, A2AR, and β3AR in white adipose tissue.Conclusions: EA reduced food intake, BW, TG, and cholesterol, and improved glucose tolerance in HFD mice. This ameliorative effect of EA on obesity-related symptoms associated with its promoted adipose tissue plasticity via activating sympathetic nerves.

Objective: This study investigated the influence of electroacupuncture (EA) and its potential underlying mechanisms on adipose tissue in obese mice. Methods: Three-week-old male C56BL/6 mice were randomly divided to feed or not to feed high-fat diet (HFD), named HFD group and chow diet (CD) group, respectively. After 12 weeks, CD and HFD mice were randomly divided into two groups, respectively, to receive or not receive EA for 4 weeks. Body weight (BW) was monitored. Intraperitoneal glucose tolerance test and metabolic chamber recordings were performed. Blood samples and adipose tissue were collected for the analysis of leptin, triglyceride levels, and fat browning-related proteins. Results: EA significantly reduced food intake, BW, and white adipose tissue (WAT)/BW ratio; decreased the adipocyte size and serum concentrations of triglyceride (TG) and cholesterol; and increased oxygen consumption in HFD mice. Compared with the CD mice, the HFD mice had elevated fasting serum glucose level and impaired glucose tolerance; however, these parameters were decreased by EA treatment. Meanwhile, EA promoted the protein and mRNA expressions of UCP1, PRDM16, and PGC-1α in adipose tissue, and activated sympathetic nerves via p-TH, A2AR, and β3AR in white adipose tissue. Conclusions: EA reduced food intake, BW, TG, and cholesterol, and improved glucose tolerance in HFD mice. This ameliorative effect of EA on obesity-related symptoms associated with its promoted adipose tissue plasticity via activating sympathetic nerves. [ABSTRACT FROM AUTHOR]