A Possible Inflammatory Role of Twist1 in Human White Adipocytes

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes “browning” of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.

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Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats

Diabetes ◽

10.2337/diabetes.49.1.20 ◽

2000 ◽

Vol 49 (1) ◽

pp. 20-24 ◽

Cited By ~ 29

Author(s):

J. T. Cheng ◽

I. M. Liu ◽

T. C. Chi ◽

K. Shinozuka ◽

F. H. Lu ◽

...

Keyword(s):

Wistar Rats ◽

White Adipocytes

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Expression of GPR43 in Brown Adipogenesis Is Enhanced by Rosiglitazone and Controlled by PPARγ/RXR Heterodimerization

PPAR Research ◽

10.1155/2018/1051074 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Jiamiao Hu ◽

Arong Zhou ◽

Peter C. K. Cheung ◽

Baodong Zheng ◽

Shaoxiao Zeng ◽

...

Keyword(s):

Adipocyte Differentiation ◽

Late Phase ◽

Short Chain Fatty Acids ◽

Brown Adipocyte ◽

Biological Functions ◽

Brown Adipocytes ◽

White Adipocytes ◽

G Protein Coupled ◽

Brown Adipogenesis

GPR43, a G-protein coupled receptor recognizing short-chain fatty acids, has been reported to participate in many biological functions of white adipocytes, such as adipogenesis and lipolysis. However, the functional role of GPR43 in brown adipocytes is still not clear. In this study, we investigated the effects of the PPARγ agonist rosiglitazone on GPR43 expression in brown adipogenesis. The results demonstrated that GPR43 was expressed during the late phase of brown adipocyte differentiation, which could be further augmented by adipogenic agent rosiglitazone treatment. The PPARγ/RXR heterodimerization was found to be the key transcription factor for this enhancing effect of rosiglitazone on GPR43 expression. Taken together, these results suggested GPR43 levels might be regulated by PPARγ-activated events during brown adipocytes differentiation and reflect the adipogenesis status of brown adipocytes.

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Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates

10.1101/524868 ◽

2019 ◽

Author(s):

Devjanee Swain-Lenz ◽

Alejandro Berrio ◽

Alexias Safi ◽

Gregory E. Crawford ◽

Gregory A. Wray

Keyword(s):

Adipose Tissue ◽

Body Fat ◽

White Adipose Tissue ◽

Sequence Motif ◽

Primary Role ◽

Regulatory Regions ◽

Comparative Analyses ◽

White Adipocytes ◽

Beige Adipocytes

AbstractHumans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using macaque as an outgroup. We find that many cis-regulatory regions that are specifically closed in humans are under positive selection, located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which white adipocytes are transdifferentiated into beige adipocytes. While the primary role of white adipocytes is to store lipids, beige adipocytes are thermogeneic. The collective closing of many putative regulatory regions associated with beiging of fat suggests an adaptive mechanism that increases body fat in humans.

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Abscisic Acid: A Conserved Hormone in Plants and Humans and a Promising Aid to Combat Prediabetes and the Metabolic Syndrome

Nutrients ◽

10.3390/nu12061724 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1724

Author(s):

Mirko Magnone ◽

Laura Sturla ◽

Lucrezia Guida ◽

Sonia Spinelli ◽

Giulia Begani ◽

...

Keyword(s):

Metabolic Syndrome ◽

Abscisic Acid ◽

Glucose Uptake ◽

Metabolic Response ◽

The Metabolic Syndrome ◽

White Adipocytes ◽

Living Organisms ◽

Glucose Availability

Abscisic acid (ABA) is a hormone with a very long evolutionary history, dating back to the earliest living organisms, of which modern (ABA-producing) cyanobacteria are likely the descendants, well before separation of the plant and animal kingdoms, with a conserved role as a signal regulating cell responses to environmental challenges. In mammals, nanomolar ABA controls the metabolic response to glucose availability by stimulating glucose uptake in skeletal muscle and adipose tissue with an insulin-independent mechanism and increasing energy expenditure in the brown and white adipose tissues. Activation by ABA of AMP-dependent kinase (AMPK), in contrast to the insulin-induced activation of AMPK-inhibiting Akt, is responsible for stimulation of GLUT4-mediated muscle glucose uptake, and for the browning effect on white adipocytes. Intake of micrograms per Kg body weight of ABA improves glucose tolerance in both normal and in borderline subjects and chronic intake of such a dose of ABA improves blood glucose, lipids and morphometric parameters (waist circumference and body mass index) in borderline subjects for prediabetes and the metabolic syndrome. This review summarizes the most recent results obtained in vivo with microgram amounts of ABA, the role of the receptor LANCL2 in the hormone’s action and the significance of the endowment by mammals of two different hormones controlling the metabolic response to glucose availability. Finally, open issues in need of further investigation and perspectives for the clinical use of nutraceutical ABA are discussed.

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On the role of macrophages in the control of adipocyte energy metabolism

Endocrine Connections ◽

10.1530/ec-19-0016 ◽

2019 ◽

Vol 8 (6) ◽

pp. R105-R121 ◽

Cited By ~ 3

Author(s):

Michaela Keuper

Keyword(s):

Adipose Tissue ◽

Mitochondrial Function ◽

Current Knowledge ◽

Human Adipose Tissue ◽

White Adipocytes ◽

Secreted Factors ◽

Adipose Tissue Macrophages

The crosstalk between macrophages (MΦ) and adipocytes within white adipose tissue (WAT) influences obesity-associated insulin resistance and other associated metabolic disorders, such as atherosclerosis, hypertension and type 2 diabetes. MΦ infiltration is increased in WAT during obesity, which is linked to decreased mitochondrial content and activity. The mechanistic interplay between MΦ and mitochondrial function of adipocytes is under intense investigation, as MΦ and inflammatory pathways exhibit a pivotal role in the reprogramming of WAT metabolism in physiological responses during cold, fasting and exercise. Thus, the underlying immunometabolic pathways may offer therapeutic targets to correct obesity and metabolic disease. Here, I review the current knowledge on the quantity and the quality of human adipose tissue macrophages (ATMΦ) and their impact on the bioenergetics of human adipocytes. The effects of ATMΦ and their secreted factors on mitochondrial function of white adipocytes are discussed, including recent research on MΦ as part of an immune signaling cascade involved in the ‘browning’ of WAT, which is defined as the conversion from white, energy-storing adipocytes into brown, energy-dissipating adipocytes.

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Differentiation of Human Induced Pluripotent Stem Cells into Brown and White Adipocytes: Role of Pax3

Stem Cells ◽

10.1002/stem.1607 ◽

2014 ◽

Vol 32 (6) ◽

pp. 1459-1467 ◽

Cited By ~ 44

Author(s):

Tala Mohsen-Kanson ◽

Anne-Laure Hafner ◽

Brigitte Wdziekonski ◽

Yasuhiro Takashima ◽

Phi Villageois ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

White Adipocytes ◽

Induced Pluripotent

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Transdifferentiation properties of adipocytes in the adipose organ

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00183.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. E977-E986 ◽

Cited By ~ 213

Author(s):

Saverio Cinti

Keyword(s):

Insulin Resistance ◽

Visceral Fat ◽

Metabolic Disorders ◽

Subcutaneous Fat ◽

Causative Factor ◽

Brown Adipocytes ◽

Anatomy And Physiology ◽

White Adipocytes ◽

Adipose Organ

Mammals have two types of adipocytes, white and brown, but their anatomy and physiology is different. White adipocytes store lipids, and brown adipocytes burn them to produce heat. Previous descriptions implied their localization in distinct sites, but we demonstrated that they are mixed in many depots, raising the concept of adipose organ. We explain the reason for their cohabitation with the hypothesis of reversible physiological transdifferentiation; they are able to convert one into each other. If needed, the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ associates with resistance to obesity and related disorders. Another example of physiological transdifferetiation of adipocytes is offered by the mammary gland; the pregnancy hormonal stimuli seems to trigger a reversible transdifferentiation of adipocytes into milk-secreting epithelial glands. The obese adipose organ is infiltrated by macrophages inducing chronic inflamation that is widely considered as a causative factor for insulin resistance. We showed that the vast majority of macrophages infiltrating the obese organ are arranged around dead adipocytes, forming characteristic crown-like structures. We recently found that visceral fat is more infiltrated than the subcutaneous fat despite a smaller size of visceral adipocytes. This suggests a different susceptibility of visceral and subcutaneous adipocytes to death, raising the concept of smaller critical death size that could be important to explain the key role of visceral fat for the metabolic disorders associated with obesity.

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Ginsenoside Rg3 Induces Browning of 3T3-L1 Adipocytes by Activating AMPK Signaling

Nutrients ◽

10.3390/nu12020427 ◽

2020 ◽

Vol 12 (2) ◽

pp. 427 ◽

Cited By ~ 2

Author(s):

Kyungtae Kim ◽

Ki Hong Nam ◽

Sang Ah Yi ◽

Jong Woo Park ◽

Jeung-Whan Han ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Panax Ginseng ◽

Lipid Droplets ◽

Adenosine Monophosphate ◽

Underlying Mechanism ◽

Therapeutic Effects ◽

Ginsenoside Rg3 ◽

White Adipocytes

Ginsenoside Rg3, one of the major components in Panax ginseng, has been reported to possess several therapeutic effects including anti-obesity properties. However, its effect on the browning of mature white adipocytes as well as the underlying mechanism remains poorly understood. In this study, we suggested a novel role of Rg3 in the browning of mature 3T3-L1 adipocytes by upregulating browning-related gene expression. The browning effects of Rg3 on differentiated 3T3-L1 adipocytes were evaluated by analyzing browning-related markers using quantitative PCR, immunoblotting, and immunostaining. In addition, the size and sum area of lipid droplets in differentiated 3T3-L1 adipocytes were measured using Oil-Red-O staining. In mature 3T3-L1 adipocytes, Rg3 dose-dependently induced the expression of browning-related genes such as Ucp1, Prdm16, Pgc1α, Cidea, and Dio2. Moreover, Rg3 induced the expression of beige fat-specific genes (CD137 and TMEM26) and lipid metabolism-associated genes (FASN, SREBP1, and MCAD), which indicated the activation of lipid metabolism by Rg3. We also demonstrated that activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) is required for Rg3-mediated up-regulation of browning gene expression. Moreover, Rg3 inhibited the accumulation of lipid droplets and reduced the droplet size in mature 3T3-L1 adipocytes. Taken together, this study identifies a novel role of Rg3 in browning of white adipocytes, as well as suggesting a potential mechanism of an anti-obesity effect of Panax ginseng.

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Insulin increases the density of potassium channels in white adipocytes: possible role in adipogenesis

Journal of Endocrinology ◽

10.1677/joe.0.1740299 ◽

2002 ◽

Vol 174 (2) ◽

pp. 299-307 ◽

Cited By ~ 8

Author(s):

MP Ramirez-Ponce ◽

JC Mateos ◽

JA Bellido

Keyword(s):

Potassium Channels ◽

Normal Growth ◽

Potassium Currents ◽

High Concentration ◽

Differentiated Cells ◽

White Adipocytes ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Inhibition Of Differentiation

We studied the potassium currents in white adipocytes obtained by culturing preadipocytes from rat epididymal tissue, both with insulin (WA(i)) and without insulin (WA(o)), in order to test the role of insulin in the development of voltage-gated potassium channels (K(v)) during adipogenesis. Occasionally, very small potassium currents (I(K,V)) were present in preadipocytes; however these currents were measured in all differentiated cells (adipocytes). WA(i) exhibited greater macroscopic potassium currents than WA(o) with no apparent differences in kinetics or voltage dependence. The current density (pA/ micro m(2)) calculated in WA(i) was higher than in WA(o). Currents were blocked by millimolar concentrations of tetrethylamonium (TEA). The effect of insulin on adipogenesis, both with and without TEA, was analysed. Four days without insulin and three days with insulin were necessary to increase the total number of cells in culture by 2.5-fold. Insulin increased the number of differentiated cells by 73.5%. Cell proliferation and differentiation were inhibited by TEA. Proliferation was affected only by high concentration of TEA. Inhibition of differentiation was dose dependent, with the concentration necessary for half-block similar to the IC(50) values to block potassium channels. These results suggest that insulin increases the density of K(v) and that these channels may be necessary for the normal growth of white adipocytes in culture.

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