scholarly journals Gpr1 is an active chemerin receptor influencing glucose homeostasis in obese mice

2014 ◽  
Vol 222 (2) ◽  
pp. 201-215 ◽  
Author(s):  
Jillian L Rourke ◽  
Shanmugam Muruganandan ◽  
Helen J Dranse ◽  
Nichole M McMullen ◽  
Christopher J Sinal
Keyword(s):  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Stromal Vascular Fraction ◽  
Tolerance Test ◽  
Glucose Levels ◽  
Brown Adipose ◽  
Elevated Glucose ◽  
And Function ◽  
G Protein Coupled

Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murineGpr1mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) andCmklr1,Gpr1expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygousGpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lackingGpr1exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects ofGpr1deficiency on adiposity, energy balance, and glucose homeostasisin vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

scholarly journals A Change in Liver Metabolism but Not in Brown Adipose Tissue Thermogenesis Is an Early Event in Ovariectomy-Induced Obesity in Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2881-2891 ◽  
Author(s):  
Mariana Nigro ◽  
Anderson T. Santos ◽  
Clarissa S. Barthem ◽  
Ruy A. N. Louzada ◽  
Rodrigo S. Fortunato ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Tolerance Test ◽  
Uncoupling Protein 1 ◽  
Ovx Rats ◽  
Bat Mitochondria ◽  
Brown Adipose

Menopause is associated with increased visceral adiposity and disrupted glucose homeostasis, but the underlying molecular mechanisms related to these metabolic changes are still elusive. Brown adipose tissue (BAT) plays a key role in energy expenditure that may be regulated by sexual steroids, and alterations in glucose homeostasis could precede increased weight gain after ovariectomy. Thus, the aim of this work was to evaluate the metabolic pathways in both the BAT and the liver that may be disrupted early after ovariectomy. Ovariectomized (OVX) rats had increased food efficiency as early as 12 days after ovariectomy, which could not be explained by differences in feces content. Analysis of isolated BAT mitochondria function revealed no differences in citrate synthase activity, uncoupling protein 1 expression, oxygen consumption, ATP synthesis, or heat production in OVX rats. The addition of GDP and BSA to inhibit uncoupling protein 1 decreased oxygen consumption in BAT mitochondria equally in both groups. Liver analysis revealed increased triglyceride content accompanied by decreased levels of phosphorylated AMP-activated protein kinase and phosphorylated acetyl-CoA carboxylase in OVX animals. The elevated expression of gluconeogenic enzymes in OVX and OVX + estradiol rats was not associated with alterations in glucose tolerance test or in serum insulin but was coincident with higher glucose disposal during the pyruvate tolerance test. Although estradiol treatment prevented the ovariectomy-induced increase in body weight and hepatic triglyceride and cholesterol accumulation, it was not able to prevent increased gluconeogenesis. In conclusion, the disrupted liver glucose homeostasis after ovariectomy is neither caused by estradiol deficiency nor is related to increased body mass.

Role of bone morphogenetic protein 4 in the differentiation of brown fat-like adipocytes

2014 ◽  
Vol 306 (4) ◽  
pp. E363-E372 ◽  
Author(s):  
Ruidan Xue ◽  
Yun Wan ◽  
Shuo Zhang ◽  
Qiongyue Zhang ◽  
Hongying Ye ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
White Adipocyte ◽  
Brown Adipose ◽  
And Function ◽  
Brown Adipogenesis

There are two different types of fat present in mammals: white adipose tissue, the primary site of energy storage, and brown adipose tissue, which is specializes in energy expenditure. Factors that specify the developmental fate and function of brown fat are poorly understood. Bone morphogenic proteins (BMPs) play an important role in adipogenesis. While BMP4 is capable of triggering commitment of stem cells to the white adipocyte lineage, BMP7 triggers commitment of progenitor cells to a brown adipocyte lineage and activates brown adipogenesis. To investigate the differential effects of BMPs on the development of adipocytes, C3H10T1/2 pluripotent cells were pretreated with BMP4 and BMP7, followed by different adipogenic induction cocktails. Both BMP4 and BMP7 unexpectedly activated a full program of brown adipogenesis, including induction of the brown fat-defining marker uncoupling protein-1 (UCP1), increasing the expression of early regulators of brown fat fate PRDM16 (PR domain-containing 16) and induction of mitochondrial biogenesis and function. Implantation of BMP4-pretreated C3H10T1/2 cells into nude mice resulted in the development of adipose tissue depots containing UCP1-positive brown adipocytes. Interestingly, BMP4 could also induce brown fat-like adipocytes in both white and brown preadipocytes, thereby decreasing the classical brown adipocyte marker Zic1 and increasing the recently identified beige adipocyte marker TMEM26. The data indicate an important role for BMP4 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro and offers a potentially new therapeutic approach for the treatment of obesity.

scholarly journals Empagliflozin Induces White Adipocyte Browning and Modulates Mitochondrial Dynamics in KK Cg-Ay/J Mice and Mouse Adipocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Linxin Xu ◽  
Chaofei Xu ◽  
Xiangyang Liu ◽  
Xiaoyu Li ◽  
Ting Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Compound C ◽  
Kkay Mice ◽  
Brown Adipose ◽  
And Function

Background: White adipose tissue (WAT) browning is a promising target for obesity prevention and treatment. Empagliflozin has emerged as an agent with weight-loss potential in clinical and in vivo studies, but the mechanisms underlying its effect are not fully understood. Here, we investigated whether empagliflozin could induce WAT browning and mitochondrial alterations in KK Cg-Ay/J (KKAy) mice, and explored the mechanisms of its effects.Methods: Eight-week-old male KKAy mice were administered empagliflozin or saline for 8 weeks and compared with control C57BL/6J mice. Mature 3T3-L1 adipocytes were treated in the presence or absence of empagliflozin. Mitochondrial biosynthesis, dynamics, and function were evaluated by gene expression analyses, fluorescence microscopy, and enzymatic assays. The roles of adenosine monophosphate–activated protein kinase (AMPK) and peroxisome proliferator–activated receptor-γ coactivator-1-alpha (PGC-1α) were determined through AICAR (5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside)/Compound C and RNA interference, respectively.Results: Empagliflozin substantially reduced the bodyweight of KKAy mice. Mice treated with empagliflozin exhibited elevated cold-induced thermogenesis and higher expression levels of uncoupling protein 1 (UCP1) and other brown adipose tissue signature proteins in epididymal and perirenal WAT, which was an indication of browning in these WAT depots. At the same time, empagliflozin enhanced fusion protein mitofusin 2 (MFN2) expression, while decreasing the levels of the fission marker phosphorylated dynamin-related protein 1 (Ser616) [p-DRP1 (Ser616)] in epididymal and perirenal WAT. Empagliflozin also increased mitochondrial biogenesis and fusion, improved mitochondrial integrity and function, and promoted browning of 3T3-L1 adipocytes. Further, we found that AMPK signaling activity played an indispensable role in empagliflozin-induced browning and mitochondrial biogenesis, and that PGC-1α was required for empagliflozin-induced fusion. Whether empagliflozin activates AMPK by inhibition of SGLT2 or by independent mechanisms remains to be tested.Conclusion: Our results suggest that empagliflozin is a promising anti-obesity treatment, which can immediately induce WAT browning mitochondrial biogenesis, and regulate mitochondrial dynamics.

scholarly journals Identification and characterization of distinct murine brown adipocyte lineages

2020 ◽  
Author(s):  
Ruth Karlina ◽  
Dominik Lutter ◽  
Viktorian Miok ◽  
David Fischer ◽  
Irem Altun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Stromal Vascular Fraction ◽  
Gene Expression Profiles ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Body Energy

AbstractBrown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. While increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Using single cell RNA sequencing of the stromal vascular fraction of murine BAT and analysis of 67 brown preadipocyte and adipocyte clones we unravel heterogeneity within brown preadipocytes. Statistical analysis of gene expression profiles from these clones identifies markers distinguishing brown adipocyte lineages. We confirm the presence of distinct brown adipocyte populations in vivo using three identified markers; Eif5, Tcf25, and Bin1. Functionally, we demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that Bin1 marks a dormant brown adipocyte type. The existence of multiple brown adipocyte lineages suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct function in thermogenesis and the regulation of whole body energy homeostasis.

scholarly journals Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice

2020 ◽  
Vol 4 (1) ◽  
pp. e202000924
Author(s):  
Ruth Karlina ◽  
Dominik Lutter ◽  
Viktorian Miok ◽  
David Fischer ◽  
Irem Altun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Stromal Vascular Fraction ◽  
Gene Expression Profiles ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Brown Adipose

Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.

scholarly journals Treatment With Atrial Natriuretic Peptide Induces Adipose Tissue Browning and Exerts Thermogenic Actions in Vivo.

2021 ◽  
Author(s):  
Haruka Kimura ◽  
Tomohisa Nagoshi ◽  
Yuhei Oi ◽  
Akira Yoshii ◽  
Yoshiro Tanaka ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Cold Exposure ◽  
Lipid Droplets ◽  
Tolerance Test ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Tissue Browning

Abstract Background: Although natriuretic peptides (NPs) classically act on the renal and cardiovascular systems, increasing evidence suggests that NPs also largely coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported that A-type NP (ANP) raises the intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether or not exogenous ANP treatment exerts a significant impact on adipose tissues in vivo using diet-induced obese mice.Methods and Results: C57BL/6 mice fed a high-fat diet (HFD) or normal-fat diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously via osmotic pump for another 3 weeks (0.5 μg/kg/min). The intraperitoneal glucose tolerance test and insulin tolerance test showed that ANP treatment significantly ameliorated HFD-induced insulin resistance. Histological analyses revealed that HFD increased the brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT (eWAT), and hepatic steatosis, all of which were substantially attenuated by ANP treatment. Likewise, ANP treatment markedly increased the expression of uncoupling protein-1 (UCP1), a specific marker of BAT, in iWAT (browning). ANP also further increased the UCP1 expression in BAT with an NFD. Accordingly, the cold tolerance test (at 4 °C for 4 h) demonstrated that the ANP-treated mice were tolerant to cold exposure.Conclusions: Exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis as well as by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.

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