Spatial Recruitment of Cardiolipins in Inguinal White Adipose Tissue after Cold Stimulation is Independent of UCP1

Abstract Background: Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves help regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration, and plasticity, including neurite outgrowth and synapse formation. Peripheral immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose SVF secretes brain derived neurotrophic factor (BDNF). Methods: We now show that deletion of this neurotrophic factor from the myeloid lineage of immune cells led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation. Results: We and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C+ CCR2+ Cx3CR1+ monocytes/macrophages that express noradrenergic receptors and BDNF. This subset of myeloid lineage cells also clearly interacted with peripheral nerves in the scWAT and were therefore considered neuroimmune cells. Conclusions: We propose that these myeloid lineage, cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.

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Spexin Friend or Foe? Novel Role of Spexin During Thermogenesis of White Adipose Tissue

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.117 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A58-A58

Author(s):

Sabrina E Gambaro ◽

Guillermina Maria Zubiria ◽

Alejandra P Giordano ◽

Ezequiel A Harnichar ◽

Andrea E Portales ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Cold Exposure ◽

Interaction Effect ◽

Caloric Intake ◽

Relative Mass ◽

Diabetic Patients ◽

Cold Stimulation

Abstract Spexin (SPX) is a novel adipokine playing an emerging role in metabolic diseases due to its involvement in carbohydrate homeostasis, weight loss, appetite control, gastrointestinal movement, among others. Moreover, plasma levels are reduced in obese and type II diabetic patients. In vitro, SPX favors lipolysis in adipocytes and hepatocytes and inhibits white adipogenesis. Therefore, the aim of this study was to evaluate the role of SPX in white adipose tissue (AT) thermogenesis. C57BL/6J male mice were treated or not with SPX for ten days (ip. 29 µg/kg/day; CTR and SPX). At day 3 mice were randomly divided: a group was kept at room temperature (RT) and the other at 4°C to stimulate thermogenesis (CTR-C and SPX-C). Caloric intake and body weight was daily recorded. At the end of the protocol plasma, Brown AT (BAT), abdominal AT (Epidydimal, EAT) and subcutaneous AT (Inguinal, IAT) depots were collected for several measurements. We found that caloric intake was increased when animals were exposed to cold (P<0.001). Body weight change revealed a differential effect of SPX depending on temperature (interaction SPX x Cold, P<0.05): SPX animals weighted less than CTR at RT, but upon cold stimulation there was no difference. No changes were observed for plasma glucose levels, however plasma triglycerides (Tg) levels decreased after cold exposure regardless SPX treatment (Cold P<0.01). Liver Tg content showed a SPX x Cold interaction effect (P<0.0001), where, upon cold stimulation, CTR-C animals increased their levels, but on the contrary SPX-C mice decreased it. EAT, IAT and BAT relative mass showed an interaction effect of variables (SPX x Cold P<0.05). When compared upon cold, SPX-C mice had less AT mass compared to CTR-C mice. IAT and EAT mRNA expression of UCP1 and Cox8b showed SPX x Cold interaction (P<0.05), with a tendency of reduction or no difference in SPX at RT, but with a significant decrease in SPX-C compared to CTR-C mice upon cold exposure. PGC1a expression was increased in EAT from cold exposed-mice and in IAT only in CTR-C mice. UCP1 protein levels showed different results depending on the AT depot. For IAT SPX x Cold interaction (P<0.05) was observed, where SPX inhibited UCP1 stimulation only upon cold exposure. On the contrary, for EAT UCP1 levels decreased in SPX-treated mice, regardless cold exposure (SPX P<0.05). In conclusion, SPX treatment in vivo reduced the thermogenic process in subcutaneous and abdominal AT, being more evident upon cold stimulation. PICT2017-2038, PICT2017-2314.

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The involvement of neuroimmune cells in adipose innervation

Molecular Medicine ◽

10.1186/s10020-020-00254-3 ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Magdalena Blaszkiewicz ◽

Elizabeth Wood ◽

Sigi Koizar ◽

Jake Willows ◽

Ryan Anderson ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Cold Exposure ◽

Immune Cells ◽

Neurotrophic Factors ◽

Neurotrophic Factor ◽

Stromal Vascular Fraction ◽

Proper Function ◽

Cold Stimulation ◽

Myeloid Lineage

Abstract Background Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration, and plasticity, including neurite outgrowth and synapse formation. Peripheral immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose SVF secretes brain derived neurotrophic factor (BDNF). Methods We now show that deletion of this neurotrophic factor from the myeloid lineage of immune cells led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation. Results We and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C+ CCR2+ Cx3CR1+ monocytes/macrophages that express noradrenergic receptors and BDNF. This subset of myeloid lineage cells also clearly interacted with peripheral nerves in the scWAT and were therefore considered neuroimmune cells. Conclusions We propose that these myeloid lineage, cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.

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The Involvement of Neuroimmune Cells in Adipose Innervation

10.21203/rs.3.rs-66882/v1 ◽

2020 ◽

Author(s):

Magdalena Blaszkiewicz ◽

Elizabeth Wood ◽

Sigi Koizar ◽

Jake Willows ◽

Ryan Anderson ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Cold Exposure ◽

Immune Cells ◽

Neurotrophic Factors ◽

Neurotrophic Factor ◽

Stromal Vascular Fraction ◽

Cell Number ◽

Proper Function ◽

Cold Stimulation

Abstract Background: Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration and plasticity, including neurite outgrowth and synapse formation. Peripheral blood immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose immune cells secrete brain derived neurotrophic factor (BDNF). Methods: We now show that deletion of this neurotrophic factor from the myeloid lineage led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation. Results: We and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C + CCR2 + Cx3CR1 + monocytes/macrophages that express noradrenergic receptors and BDNF. Conclusions: We propose that these cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.

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SCD1 promotes lipid mobilization in subcutaneous white adipose tissue

The Journal of Lipid Research ◽

10.1194/jlr.ra120000869 ◽

2020 ◽

Vol 61 (12) ◽

pp. 1589-1604

Author(s):

Ying Zou ◽

Yi-Na Wang ◽

Hong Ma ◽

Zhi-Hui He ◽

Yan Tang ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Lipid Synthesis ◽

Hormone Sensitive Lipase ◽

Cold Stimulation ◽

Lipid Mobilization ◽

Subcutaneous White Adipose Tissue ◽

Beneficial Effects ◽

Beige Adipocytes

Beiging of white adipose tissue (WAT) has beneficial effects on metabolism. Although it is known that beige adipocytes are active in lipid catabolism and thermogenesis, how they are regulated deserves more explorations. In this study, we demonstrate that stearoyl-CoA desaturase 1 (SCD1) in subcutaneous WAT (scWAT) responded to cold stimulation and was able to promote mobilization of triacylglycerol [TAG (triglyceride)]. In vitro studies showed that SCD1 promoted lipolysis in C3H10T1/2 white adipocytes. The lipolytic effect was contributed by one of SCD1’s products, oleic acid (OA). OA upregulated adipose TAG lipase and hormone-sensitive lipase expression. When SCD1 was overexpressed in the scWAT of mice, lipolysis was enhanced, and oxygen consumption and heat generation were increased. These effects were also demonstrated by the SCD1 knockdown experiments in mice. In conclusion, our study suggests that SCD1, known as an enzyme for lipid synthesis, plays a role in upregulating lipid mobilization through its desaturation product, OA.

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The involvement of neuroimmune cells in adipose innervation

10.1101/787234 ◽

2019 ◽

Cited By ~ 1

Author(s):

Magdalena Blaszkiewicz ◽

Elizabeth Wood ◽

Sigi Koizar ◽

Jake Willows ◽

Ryan Anderson ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Cold Exposure ◽

Immune Cells ◽

Neurotrophic Factors ◽

Neurotrophic Factor ◽

Stromal Vascular Fraction ◽

Cell Number ◽

Proper Function ◽

Cold Stimulation

AbstractBackgroundInnervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration and plasticity, including neurite outgrowth and synapse formation. Peripheral blood immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose immune cells secrete brain derived neurotrophic factor (BDNF).MethodsWe now show that deletion of this neurotrophic factor from the myeloid lineage led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation.ResultsWe and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C + CCR2 + Cx3CR1 + monocytes/macrophages that express noradrenergic receptors and BDNF.ConclusionsWe propose that these cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.

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