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10 pages, 943 KiB

Open AccessArticle

The Expression of Adipose Tissue-Derived Cardiotrophin-1 in Humans with Obesity

by Jacqueline Stephens, Eric Ravussin and Ursula White

Biology 2019, 8(2), 24; https://doi.org/10.3390/biology8020024 - 13 Apr 2019

Cited by 8 | Viewed by 3470

Abstract

Cardiotrophin-1 (CT-1) is a gp130 cytokine that was previously characterized for its effects on cardiomyocytes and identified as a marker of heart failure. More recent studies reported elevated circulating levels of CT-1 in humans with obesity and metabolic syndrome (MetS). However, a subsequent [...] Read more.

Cardiotrophin-1 (CT-1) is a gp130 cytokine that was previously characterized for its effects on cardiomyocytes and identified as a marker of heart failure. More recent studies reported elevated circulating levels of CT-1 in humans with obesity and metabolic syndrome (MetS). However, a subsequent rodent study implicated CT-1 as a potential therapeutic target for obesity and MetS. Adipose tissue (AT) is broadly acknowledged as an endocrine organ and is a substantial source of CT-1. However, no study has examined the expression of adipose-derived CT-1 in humans. We present the first analysis of CT-1 mRNA expression in subcutaneous AT and its association with clinical variables in 22 women with obesity and 15 men who were 40% overfed for 8-weeks. We observed that CT-1 expression was higher in the subcutaneous abdominal (scABD) than the femoral (scFEM) depot. Importantly, we reveal that scFEM but not scABD, CT-1 expression was negatively associated with visceral adiposity and intrahepatic lipid, while positively correlated with insulin sensitivity in obese women. Also, men with higher CT-1 levels at baseline had less of a decline in insulin sensitivity in response to overfeeding. Our data provide new knowledge on the regulation of adipose-derived CT-1 in obesity and during weight gain in response to overfeeding in humans and suggest that CT-1 may play a protective role in obesity and related disorders. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

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10 pages, 2596 KiB

Open AccessArticle

Oncostatin M Mediates Adipocyte Expression and Secretion of Stromal-Derived Factor 1

by Hardy Hang, Jennifer L. Bailey and Carrie M. Elks

Biology 2019, 8(1), 19; https://doi.org/10.3390/biology8010019 - 23 Mar 2019

Cited by 5 | Viewed by 3870

Abstract

Adipose tissue homeostasis depends on interactions between stromal cells, adipocytes, and the cytokines and chemokines they produce. The gp130 cytokine, oncostatin M (OSM), plays a role in adipose tissue homeostasis. Mice, lacking the OSM receptor (OSMR) in adipocytes (Osmr^FKO mice), exhibit [...] Read more.

Adipose tissue homeostasis depends on interactions between stromal cells, adipocytes, and the cytokines and chemokines they produce. The gp130 cytokine, oncostatin M (OSM), plays a role in adipose tissue homeostasis. Mice, lacking the OSM receptor (OSMR) in adipocytes (Osmr^FKO mice), exhibit derangements in adipose tissue, insulin sensitivity, and immune cell balance. Here, we describe a possible role for the chemokine stromal-derived factor 1 (SDF-1) in these alterations. We treated 3T3-L1 adipocytes with OSM and observed a suppression of SDF-1 gene expression and protein secretion, an effect which was partially blunted by OSMR knockdown. However, Osmr^FKO mice also exhibited decreased SDF-1 gene and protein expression in adipose tissue. These contrasting results suggest that the loss of adipocyte OSM–OSMR signaling in vivo may be indirectly affecting adipokine production and secretion by altering OSM target genes to ultimately decrease SDF-1 expression in the Osmr^FKO mouse. We conclude that adipocyte OSM–OSMR signaling plays a role in adipose tissue SDF-1 production and may mitigate its effects on adipose tissue homeostasis. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

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Review

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16 pages, 272 KiB

Open AccessReview

Beige Fat, Adaptive Thermogenesis, and Its Regulation by Exercise and Thyroid Hormone

by Kevin J. Phillips

Biology 2019, 8(3), 57; https://doi.org/10.3390/biology8030057 - 31 Jul 2019

Cited by 17 | Viewed by 5269

Abstract

While it is now understood that the proper expansion of adipose tissue is critically important for metabolic homeostasis, it is also appreciated that adipose tissues perform far more functions than simply maintaining energy balance. Adipose tissue performs endocrine functions, secreting hormones or adipokines [...] Read more.

While it is now understood that the proper expansion of adipose tissue is critically important for metabolic homeostasis, it is also appreciated that adipose tissues perform far more functions than simply maintaining energy balance. Adipose tissue performs endocrine functions, secreting hormones or adipokines that affect the regulation of extra-adipose tissues, and, under certain conditions, can also be major contributors to energy expenditure and the systemic metabolic rate via the activation of thermogenesis. Adipose thermogenesis takes place in brown and beige adipocytes. While brown adipocytes have been relatively well studied, the study of beige adipocytes has only recently become an area of considerable exploration. Numerous suggestions have been made that beige adipocytes can elicit beneficial metabolic effects on body weight, insulin sensitivity, and lipid levels. However, the potential impact of beige adipocyte thermogenesis on systemic metabolism is not yet clear and an understanding of beige adipocyte development and regulation is also limited. This review will highlight our current understanding of beige adipocytes and select factors that have been reported to elicit the development and activation of thermogenesis in beige cells, with a focus on factors that may represent a link between exercise and ‘beiging’, as well as the role that thyroid hormone signaling plays in beige adipocyte regulation. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

14 pages, 887 KiB

Open AccessReview

Deciphering White Adipose Tissue Heterogeneity

by Quyen Luong, Jun Huang and Kevin Y. Lee

Biology 2019, 8(2), 23; https://doi.org/10.3390/biology8020023 - 11 Apr 2019

Cited by 65 | Viewed by 15755

Abstract

Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are [...] Read more.

Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are differentially associated with insulin resistance and increased risk of metabolic disease. In addition to energy-dissipating brown and beige adipocytes, recent lineage tracing studies have demonstrated that individual adipose depots are composed of white adipocytes that are derived from distinct precursor populations, giving rise to distinct subpopulations of energy-storing white adipocytes. In this review, we discuss this developmental and functional heterogeneity of white adipocytes both between and within adipose depots. In particular, we will highlight findings from our recent manuscript in which we find and characterize three major subtypes of white adipocytes. We will discuss these data relating to the differences between subcutaneous and visceral white adipose tissue and in relationship to previous work deciphering adipocyte heterogeneity within adipose tissue depots. Finally, we will discuss the possible implications of adipocyte heterogeneity may have for the understanding of lipodystrophies. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

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16 pages, 281 KiB

Open AccessReview

Targeting White Adipose Tissue with Exercise or Bariatric Surgery as Therapeutic Strategies in Obesity

by Flávia Giolo De Carvalho and Lauren M. Sparks

Biology 2019, 8(1), 16; https://doi.org/10.3390/biology8010016 - 15 Mar 2019

Cited by 19 | Viewed by 5514

Abstract

Adipose tissue is critical to whole-body energy metabolism and has become recognized as a bona fide endocrine organ rather than an inert lipid reservoir. As such, adipose tissue is dynamic in its ability to secrete cytokines, free fatty acids, lipokines, hormones and other [...] Read more.

Adipose tissue is critical to whole-body energy metabolism and has become recognized as a bona fide endocrine organ rather than an inert lipid reservoir. As such, adipose tissue is dynamic in its ability to secrete cytokines, free fatty acids, lipokines, hormones and other factors in response to changes in environmental stimuli such as feeding, fasting and exercise. While excess adipose tissue, as in the case of obesity, is associated with metabolic complications, mass itself is not the only culprit in obesity-driven metabolic abnormalities, highlighting the importance of healthy and metabolically adaptable adipose tissue. In this review, we discuss the fundamental cellular processes of adipose tissue that become perturbed in obesity and the impact of exercise on these processes. While both endurance and resistance exercise can promote positive physiological adaptations in adipose tissue, endurance exercise has a more documented role in remodeling adipocytes, increasing adipokine secretion and fatty acid mobilization and oxidation during post-exercise compared with resistance exercise. Exercise is considered a viable therapeutic strategy for the treatment of obesity to optimize body composition, in particular as an adjuvant therapy to bariatric surgery; however, there is a gap in knowledge of the molecular underpinnings of these exercise-induced adaptations, which could provide more insight and opportunity for precision-based treatment strategies. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

29 pages, 852 KiB

Open AccessReview

Cold and Exercise: Therapeutic Tools to Activate Brown Adipose Tissue and Combat Obesity

by Carmem Peres Valgas da Silva, Diego Hernández-Saavedra, Joseph D. White and Kristin I. Stanford

Biology 2019, 8(1), 9; https://doi.org/10.3390/biology8010009 - 12 Feb 2019

Cited by 61 | Viewed by 15583

Abstract

The rise in obesity over the last several decades has reached pandemic proportions. Brown adipose tissue (BAT) is a thermogenic organ that is involved in energy expenditure and represents an attractive target to combat both obesity and type 2 diabetes. Cold exposure and [...] Read more.

The rise in obesity over the last several decades has reached pandemic proportions. Brown adipose tissue (BAT) is a thermogenic organ that is involved in energy expenditure and represents an attractive target to combat both obesity and type 2 diabetes. Cold exposure and exercise training are two stimuli that have been investigated with respect to BAT activation, metabolism, and the contribution of BAT to metabolic health. These two stimuli are of great interest because they have both disparate and converging effects on BAT activation and metabolism. Cold exposure is an effective mechanism to stimulate BAT activity and increase glucose and lipid uptake through mitochondrial uncoupling, resulting in metabolic benefits including elevated energy expenditure and increased insulin sensitivity. Exercise is a therapeutic tool that has marked benefits on systemic metabolism and affects several tissues, including BAT. Compared to cold exposure, studies focused on BAT metabolism and exercise display conflicting results; the majority of studies in rodents and humans demonstrate a reduction in BAT activity and reduced glucose and lipid uptake and storage. In addition to investigations of energy uptake and utilization, recent studies have focused on the effects of cold exposure and exercise on the structural lipids in BAT and secreted factors released from BAT, termed batokines. Cold exposure and exercise induce opposite responses in terms of structural lipids, but an important overlap exists between the effects of cold and exercise on batokines. In this review, we will discuss the similarities and differences of cold exposure and exercise in relation to their effects on BAT activity and metabolism and its relevance for the prevention of obesity and the development of type 2 diabetes. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

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23 pages, 3730 KiB

Open AccessReview

The Importance of Peripheral Nerves in Adipose Tissue for the Regulation of Energy Balance

by Magdalena Blaszkiewicz, Jake W. Willows, Cory P. Johnson and Kristy L. Townsend

Biology 2019, 8(1), 10; https://doi.org/10.3390/biology8010010 - 12 Feb 2019

Cited by 51 | Viewed by 12376

Abstract

Brown and white adipose tissues are essential for maintenance of proper energy balance and metabolic health. In order to function efficiently, these tissues require both endocrine and neural communication with the brain. Brown adipose tissue (BAT), as well as the inducible brown adipocytes [...] Read more.

Brown and white adipose tissues are essential for maintenance of proper energy balance and metabolic health. In order to function efficiently, these tissues require both endocrine and neural communication with the brain. Brown adipose tissue (BAT), as well as the inducible brown adipocytes that appear in white adipose tissue (WAT) after simulation, are thermogenic and energy expending. This uncoupling protein 1 (UCP1)-mediated process requires input from sympathetic nerves releasing norepinephrine. In addition to sympathetic noradrenergic signaling, adipose tissue contains sensory nerves that may be important for relaying fuel status to the brain. Chemical and surgical denervation studies of both WAT and BAT have clearly demonstrated the role of peripheral nerves in browning, thermogenesis, lipolysis, and adipogenesis. However, much is still unknown about which subtypes of nerves are present in BAT versus WAT, what nerve products are released from adipose nerves and how they act to mediate metabolic homeostasis, as well as which cell types in adipose are receiving synaptic input. Recent advances in whole-depot imaging and quantification of adipose nerve fibers, as well as other new research findings, have reinvigorated this field of research. This review summarizes the history of research into adipose innervation and brain–adipose communication, and also covers landmark and recent research on this topic to outline what we currently know and do not know about adipose tissue nerve supply and communication with the brain. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

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13 pages, 291 KiB

Open AccessReview

Immunometabolic Links between Estrogen, Adipose Tissue and Female Reproductive Metabolism

by Sally A. Eaton and Jaswinder K. Sethi

Biology 2019, 8(1), 8; https://doi.org/10.3390/biology8010008 - 7 Feb 2019

Cited by 25 | Viewed by 7885

Abstract

The current knowledge of sex-dependent differences in adipose tissue biology remains in its infancy and is motivated in part by the desire to understand why menopause is linked to an increased risk of metabolic disease. However, the development and characterization of targeted genetically-modified [...] Read more.

The current knowledge of sex-dependent differences in adipose tissue biology remains in its infancy and is motivated in part by the desire to understand why menopause is linked to an increased risk of metabolic disease. However, the development and characterization of targeted genetically-modified rodent models are shedding new light on the physiological actions of sex hormones in healthy reproductive metabolism. In this review we consider the need for differentially regulating metabolic flexibility, energy balance, and immunity in a sex-dependent manner. We discuss the recent advances in our understanding of physiological roles of systemic estrogen in regulating sex-dependent adipose tissue distribution, form and function; and in sex-dependent healthy immune function. We also review the decline in protective properties of estrogen signaling in pathophysiological settings such as obesity-related metaflammation and metabolic disease. It is clear that the many physiological actions of estrogen on energy balance, immunity, and immunometabolism together with its dynamic regulation in females make it an excellent candidate for regulating metabolic flexibility in the context of reproductive metabolism. Full article

(This article belongs to the Special Issue New Players in Adipocyte Biology)

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