Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review

The impact of brown adipose tissue (BAT) metabolism on understanding energy balance in humans is a relatively new and exciting field of research. The pathogenesis of obesity can be largely explained by an imbalance between caloric intake and energy expenditure, but the underlying mechanisms are far more complex. Traditional non-selective sympathetic activators have been used to artificially elevate energy utilization, or suppress appetite, however undesirable side effects are apparent with the use of these pharmacological interventions. Understanding the role of BAT, in relation to human energy homeostasis has the potential to dramatically offset the energy imbalance associated with obesity. This review discusses paradoxical effects of caffeine on peripheral adenosine receptors and the possible role of adenosine in increasing metabolism is highlighted, with consideration to the potential of central rather than peripheral mechanisms for caffeine mediated BAT thermogenesis and energy expenditure. Research on the complex physiology of adipose tissue, the embryonic lineage and function of the different types of adipocytes is summarized. In addition, the effect of BAT on overall human metabolism and the extent of the associated increase in energy expenditure are discussed. The controversy surrounding the primary β-adrenoceptor involved in human BAT activation is examined, and suggestions as to the lack of translational findings from animal to human physiology and human in vitro to in vivo models are provided. This review compares and distinguishes human and rodent BAT effects, thus developing an understanding of human BAT thermogenesis to aid lifestyle interventions targeting obesity and metabolic syndrome. The focus of this review is on the effect of BAT thermogenesis on overall metabolism, and the potential therapeutic effects of caffeine in increasing metabolism via its effects on BAT.

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The Role of Peptide Hormones Discovered in the 21st Century in the Regulation of Adipose Tissue Functions

Genes ◽

10.3390/genes12050756 ◽

2021 ◽

Vol 12 (5) ◽

pp. 756

Author(s):

Paweł A. Kołodziejski ◽

Ewa Pruszyńska-Oszmałek ◽

Tatiana Wojciechowicz ◽

Maciej Sassek ◽

Natalia Leciejewska ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

21St Century ◽

Energy Homeostasis ◽

Peptide Hormones ◽

Brown Adipose ◽

Homeostasis Regulation

Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue. In this article, we review and discuss the literature addressing the role of selected peptide hormones discovered in the 21st century (adropin, apelin, elabela, irisin, kisspeptin, MOTS-c, phoenixin, spexin, and neuropeptides B and W) in controlling white and brown adipogenesis. Furthermore, we elaborate how these hormones control adipose tissue functions in vitro and in vivo.

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Orexin Restores Aging-Related Brown Adipose Tissue Dysfunction in Male Mice

Endocrinology ◽

10.1210/en.2013-1629 ◽

2014 ◽

Vol 155 (2) ◽

pp. 485-501 ◽

Cited By ~ 55

Author(s):

Dyan Sellayah ◽

Devanjan Sikder

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Fat Mass ◽

Core Body Temperature ◽

Brown Adipocyte ◽

Aged Mice ◽

Age Related ◽

Brown Adipose ◽

The Impact

The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. In vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphologic characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy. Our results suggest a role for orexin (OX) signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.

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The PPARγ agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.91012.2008 ◽

2009 ◽

Vol 296 (5) ◽

pp. R1327-R1335 ◽

Cited By ~ 40

Author(s):

William T. Festuccia ◽

Pierre-Gilles Blanchard ◽

Véronique Turcotte ◽

Mathieu Laplante ◽

Meltem Sariahmetoglu ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Glucose Uptake ◽

Mrna Levels ◽

Pparγ Agonist ◽

Brown Adipose ◽

Lipin 1 ◽

The Impact

We investigated the mechanisms whereby peroxisome proliferator-activated receptor-γ (PPARγ) agonism affects glucose and lipid metabolism in brown adipose tissue (BAT) by studying the impact of PPARγ activation on BAT glucose uptake and metabolism, lipogenesis, and mRNA levels plus activities of enzymes involved in triacylglycerol (TAG) synthesis. Interscapular BAT of rats treated or not with rosiglitazone (15 mg·kg−1·day−1, 7 days) was evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (PAP or lipin-1), and diacylglycerol acyltransferase (DGAT). Rosiglitazone increased BAT mass without affecting whole tissue glucose uptake. BAT glycogen content (−80%), its synthesis from glucose (−50%), and mRNA levels of UDP-glucose pyrophosphorylase (−40%), which generates UDP-linked glucose for glycogen synthesis, were all reduced by rosiglitazone. In contrast, BAT TAG-glycerol synthesis in vivo and glucose incorporation into TAG-glycerol in vitro were stimulated by the agonist along with the activities and mRNA levels of glycerol 3-phosphate-generating phosphoenolpyruvate carboxykinase and glycerokinase. Furthermore, rosiglitazone markedly increased the activities of GPAT and DGAT but not those of lipin-1-mediated PAP-1, enzymes involved in the sequential acylation of glycerol 3-phosphate and TAG synthesis. Because an adequate supply of fatty acids is essential for BAT nonshivering thermogenesis, the enhanced ability of BAT to synthesize TAG under PPARγ activation may constitute an important mechanism by which lipid substrates are stored in preparation for an eventual thermogenic activation.

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White, beige and brown adipose tissue: structure, function, specific features and possibility formation and divergence in pigs

Foods and raw materials ◽

10.21603/2308-4057-2022-1-10-18 ◽

2021 ◽

pp. 10-18

Author(s):

Irina Chernukha ◽

Liliya Fedulova ◽

Elena Kotenkova

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

The Body ◽

Intermediate Form ◽

Swine Industry ◽

Brown Adipose ◽

Beige Fat ◽

White Fat ◽

The Impact

Introduction. Traditionally, mammalian adipose tissue is divided into white (white adipose tissue – WAT) and brown (brown adipose tissue – BAT). While the functions of WAT are well known as the triglyceride depot, the role of BAT in mammalian physiology has been under close investigation. The first description of the role of BAT in maintaining thermogenesis dates back to 1961. This article offers a review of structural and functional specificity of white, beige and brown adipose tissue. Results and discussion. The differences and descriptions of adipocytes and their impact on the maintenance of the main functions of the mammalian body are described in this manuscript. In particular, thermogenesis, stress response, obesity, type II diabetes. In addition to WAT and BAT, an intermediate form was also detected in the body – beige fat (BeAT or Brite). The opposite opinions regarding the presence of three types of adipose tissue in the human and animal bodies are presented. Studies on the identification of uncoupling proteins 1 and 3 and their role in the transformation of white fat into beige/brown are considered. Basically, the data on the factors of endogenous and exogenous nature on their formation are given on the example of the human body. Conclusion. With an abundance of publications on the keywords: “white, brown fat”, these studies, in the overwhelming majority, are devoted to the role of these fats in the formation of human thermogenesis, the assessment of the impact on obesity. Pigs have also been suggested to lack functional BAT, which is a major cause of neonatal death in the swine industry, therefore the focus on investigating role of different types of adipose tissue in pigs seems very promising in order to understand whether there is a compensating mechanism of thermogenesis.

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Insulin sensing by astrocytes is critical for normal thermogenesis and body temperature regulation

Journal of Endocrinology ◽

10.1530/joe-20-0052 ◽

2020 ◽

Vol 247 (1) ◽

pp. 39-52

Author(s):

Iyad H Manaserh ◽

Emily Maly ◽

Marziyeh Jahromi ◽

Lakshmikanth Chikkamenahalli ◽

Joshua Park ◽

...

Keyword(s):

Adipose Tissue ◽

Body Temperature ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Insulin Signaling ◽

Insulin Receptors ◽

Metabolic Dysregulation ◽

Brown Adipose ◽

Novel Target

The important role of astrocytes in the central control of energy balance and glucose homeostasis has recently been recognized. Changes in thermoregulation can lead to metabolic dysregulation, but the role of astrocytes in this process is not yet clear. Therefore, we generated mice congenitally lacking insulin receptors (Ir) in astrocytes (IrKOGFAP mice) to investigate the involvement of astrocyte insulin signaling. IrKOGFAP mice displayed significantly lower energy expenditure and a strikingly lower basal and fasting body temperature. When exposed to cold, however, they were able to mount a thermogenic response. IrKOGFAP mice displayed sex differences in metabolic function and thermogenesis that may contribute to the development of obesity and type II diabetes as early as 2 months of age. While brown adipose tissue exhibited higher adipocyte size in both sexes, more apoptosis was seen in IrKOGFAP males. Less innervation and lower BAR3 expression levels were also observed in IrKOGFAP brown adipose tissue. These effects have not been reported in models of astrocyte Ir deletion in adulthood. In contrast, body weight and glucose regulatory defects phenocopied such models. These findings identify a novel role for astrocyte insulin signaling in the development of normal body temperature control and sympathetic activation of BAT. Targeting insulin signaling in astrocytes has the potential to serve as a novel target for increasing energy expenditure.

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SUN-590 27-Hydroxycholesterol Triggers the Whitening of Brown Adipose Tissue

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1089 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Arvand Asghari ◽

Linh Bui ◽

Robert Stephen ◽

Michihisa Umetani

Keyword(s):

Estrogen Receptor ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

Vehicle Control ◽

The Body ◽

Wild Type ◽

Brown Adipose

Abstract 27-Hydroxycholesterol (27HC) is the most abundant oxysterol in circulation and metabolized by a P450 enzyme CYP7B1. Its levels closely correspond to those of cholesterol in the body. In addition, previously it was found that 27HC is an endogenous selective estrogen receptor modulator (SERM), which links cholesterol metabolism to estrogen receptor actions (1). Brown adipose tissue (BAT) is the primary source of energy expenditure and energy homeostasis, as well as body temperature maintenance. While previously it was believed that BAT activity is limited to neonates and young children, it is now recognized that BAT is also active in adult humans and its function is impaired by metabolic diseases such as obesity. BAT is also a secretory organ and produces brown adipokines, although the exact function of BAT and adipokines from this tissue in obesity has not been completely understood. Recently, it was reported that 27HC plays an important role in obesity and augments body weight gain in response to a high fat, high cholesterol (HFHC) diet by increasing pre-adipocyte population in the white adipose tissue. 27HC mimics the effects by HFHC diet-feeding on white adipose tissue, such as promoting the inflammation and macrophage infiltration (2). In this study, we explored the effect of 27HC on BAT morphology and function. First, we compared the morphology of BAT from wild-type mice and Cyp7b1-/- mice that have elevated levels of 27HC using H&E staining. Interestingly, brown adipocytes from Cyp7b1-/- mice were larger in cell size than those from wild-type mice, and the cells were mostly unilocular compared to the multilocular cells from wild-type mice, indicating the transition toward a “whitening” phenotype. Next, We treated mice fed a normal chow or a HFHC diet with 27HC or vehicle control for 8 weeks to examine the direct effect by 27HC on BAT. Similar to the phenotype in Cyp7b1-/-mice, 27HC increased the “whitening” of BAT regardless of the diet. We also determined the gene expression of brown adipocyte markers such as UCP1, PGC1a, and DIO2, and found that 27HC significantly decreased the expression of the BAT markers regardless of the diet, confirming the “whitening” observed in the morphology. Moreover, the energy expenditure in mice treated with 27HC was decreased compared to the vehicle control on a HFHC diet, suggesting that 27HC also alters BAT function. These results show that 27HC causes the whitening of BAT, and shed light on the important role of 27HC in brown adipose tissue function. Future experiments will be warranted toward further understanding of the role of 27HC in BAT function. Reference:(1) Umetani, Michihisa, et al. Nature medicine 13.10 (2007): 1185. (2) Asghari, Arvand, et al. Endocrinology 160.10 (2019): 2485-2494.

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Role of prolactin in lactation-induced changes in brown adipose tissue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.1.r51 ◽

1990 ◽

Vol 258 (1) ◽

pp. R51-R56 ◽

Cited By ~ 6

Author(s):

E. Chan ◽

R. Swaminathan

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Energy Utilization ◽

Serum Prolactin ◽

Enzyme Linked Immunosorbent Assay ◽

Simultaneous Administration ◽

Brown Adipose ◽

Induced Changes

During lactation the efficiency of energy utilization is increased and brown adipose tissue (BAT) thermogenesis is suppressed. We have examined the role of prolactin in the suppression of BAT during lactation in the rat. Changes in BAT were studied using an enzyme-linked immunosorbent assay for the uncoupling protein (UCP). In the first experiment BAT from pregnant and lactating rats was examined at various times. Total UPC content of BAT decreased from 364 +/- 34 to 32 +/- 9 micrograms during late lactation (20 days). Serum prolactin (PRL) concentration was elevated during lactation and was highest at 10 days. When endogenous PRL was stimulated by injection of metoclopramide (1.67 mg/kg) for 5 days, UCP content of BAT decreased by 50%. This action of metoclopramide could be blocked by simultaneous administration of bromocriptine, an inhibitor of PRL secretion. Serum PRL concentration was elevated during metoclopramide administration but not when metoclopramide and bromocriptine were given together. We conclude that PRL is a possible mediator of the suppression of BAT during lactation.

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Nutritional Regulation of Human Brown Adipose Tissue

Nutrients ◽

10.3390/nu13061748 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1748

Author(s):

Karla J. Suchacki ◽

Roland H. Stimson

Keyword(s):

Metabolic Disease ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Therapeutic Potential ◽

Metabolic Health ◽

Nutritional Regulation ◽

Increase Energy Expenditure ◽

Brown Adipose ◽

The Impact

The recent identification of brown adipose tissue in adult humans offers a new strategy to increase energy expenditure to treat obesity and associated metabolic disease. While white adipose tissue (WAT) is primarily for energy storage, brown adipose tissue (BAT) is a thermogenic organ that increases energy expenditure to generate heat. BAT is activated upon cold exposure and improves insulin sensitivity and lipid clearance, highlighting its beneficial role in metabolic health in humans. This review provides an overview of BAT physiology in conditions of overnutrition (obesity and associated metabolic disease), undernutrition and in conditions of altered fat distribution such as lipodystrophy. We review the impact of exercise, dietary macronutrients and bioactive compounds on BAT activity. Finally, we discuss the therapeutic potential of dietary manipulations or supplementation to increase energy expenditure and BAT thermogenesis. We conclude that chronic nutritional interventions may represent a useful nonpharmacological means to enhance BAT mass and activity to aid weight loss and/or improve metabolic health.

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