Adipose tissue plasticity from WAT to BAT and in between

Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticity of adipose tissue might provide new avenues for treatment of obesity-related diseases. This review will discuss the developmental origins of adipose tissue, the cellular complexity of adipose tissues, and the identification of progenitors that contribute to adipogenesis throughout development. We will touch upon the pathological remodeling of adipose tissue and discuss how our understanding of adipose tissue remodeling can uncover new therapeutic targets. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.     

Orexin-A regulates body temperature in coordination with arousal status

Orexins, hypothalamic neuropeptides, are involved in modulation of food intake and arousal status. To further examine their physiological roles in brain function, the effect of centrally administered orexin-A on body temperature was investigated in rats. Assessed by a telemetry sensor system implanted into the abdominal cavity, infusion of orexin-A into the third cerebroventricle (i3vt) increased body temperature in a dose-responsive manner. Expression of uncoupling protein 1 (UCP1) mRNA in brown adipose tissue (BAT), as a marker for peripheral thermogenesis, failed to increase after the infusion. Expression of UCP3 mRNA in skeletal muscle was up-regulated, whereas UCP2 in white adipose tissue was unchanged after the infusion. The resulting information indicates that orexin neurons regulate body temperature in coordination with arousal status independently of peripheral thermogenesis, which is regulated by BAT UCP1.     

Ethacrynic acid targets GSTM1 to ameliorate obesity by promoting browning of white adipocytes

Dear Editor, Obesity is caused by an imbalance between energy intake and expenditure,and has become a global epidemic with over 650 million adults affected.Adipose tissues in mam-mals are composed of white adipose tissue (WAT) and classical brown adipose tissue (BAT),and their balance is highly related to the occurrence of obesity.The browning of white adipocytes results in "beige" or "brite" adipocytes,which appear functionally similar to classical brown adipo-cytes,and can be detected in WAT deposits of animals that have been exposed to cold or other inducers (Fu et al.,2015).     

Three new players in energy regulation: Preptin,adropin and irisin

Homeostasis of energy is regulated by genetic factors, food intake, and energy expenditure. When energy input is greater than expenditure, the balance is positive, which can lead to weight gain and obesity. When the balance is negative, weight is lost. Regulation of this homeostasis is multi-factorial, involving many orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) peptide hormones. Peripheral tissues are now known to be involved in weight regulation and research on its endocrine characteristics proceeds apace. Preptin with 34 amino acids (MW 3948 Da), adropin with 43 amino acids and a molecular weight of (4999 Da), and irisin with 112 amino acids (12587 Da), are three newly discovered peptides critical for regulating energy metabolism. Preptin is synthesized primarily in pancreatic beta cells, and adropin mainly in the liver and brain, and many peripheral tissues. Irisin, however, is synthesized principally in the heart muscle, along with peripheral tissues, including salivary glands, kidney and liver. The prime functions of preptin and adropin include regulating carbohydrate, lipid and protein metabolisms by moderating glucose-mediated insulin release. Irisin is an anti-obesitic and anti-diabetic hormone regulating adipose tissue metabolism and glucose homeostasis by converting white to brown adipose tissue. This review offers a historical account of these discovery and function of these peptides, including their structure, and physiological and biochemical properties. Their roles in energy regulation will be discussed. Their measurement in biological fluids will be considered, which will lead to further discussion of their possible clinical value.     

Characterization of orexins (hypocretins) and melanin-concentrating hormone in genetically obese mice

Orexins (hypocretins) and the melanin-concentrating hormone (MCH) are neuropeptides localized to the lateral hypothalamic area and are potential regulators of energy homeostasis. Using highly sensitive radioimmunoassay for orexins and MCH, we determined their contents in the lateral hypothalamus (LH) of genetically obese ob/ob and db/db mice and their controls, C57BL/6J and C57BL/KSJ. The orexin contents in the lateral hypothalamus significantly increased in the ob/ob mice, whereas the orexin contents significantly decreased in the db/db mice. Mature orexin-A and -B peptides were the major endogenous orexin molecules in the lateral hypothalamus. Conversely, the MCH contents in the lateral hypothalamus of both obese mice increased compared to the control mice. MCH contents in the lateral hypothalamus were two- to five-fold higher than that of orexin contents. These results suggest that the regulatory mechanism of orexin and MCH may be different in the genetically obese mice.     

Distinction of white,beige and brown adipocytes derived from mesenchymal stem cells简

Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue (WAT) or brown adipose tissue (BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brown-like adipocytes were discovered in WAT. These brown-like adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expression pattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation (adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.     

The physiological role of orexins

Orexins/hypocretins are recently discovered neuropeptides synthetized mainly by neurons located in the posterolateral hypothalamus. Hypocretin-1 and -2 are the same peptides as orexin-A and orexin-B. Orexin A is a 33 amino acid peptide with N-terminal pyroglutamyl residue and two intrachain disulphide bonds. Orexin B is a linear peptide of 28 amino acids. These two peptides are potent agonists at both the orexin-1 (OxR1) and orexin-2 (OxR2) receptors. Orexin-A is selective ligand for OxR1 and OX2 binds both orexins. The structure of orexins and their receptors is highly conservative in mammals. Orexin A sequence is identical in several mammalian species (human, mouse, rat, bovine and porcine). Intracerebroventricular administered orexin-A stimulates food intake and energy expenditure. Orexins are also involved in the regulation of neurohormones and pituitary hormones secretion as well as in the control of cardiovascular and sleep-wake function. Orexins also play a role in the pathogenesis of narcolepsy. Mutation in the gene coding preproorexin or OxR2 receptor gene results in narcolepsy in mice and canine. In patients with narcolepsy orexin neurotransmission was altered and orexin level in cerebrospinal fluid was undetectable.     

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology

Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants. In contrast to other tissues, the embryonic origin of adipose cells remains the subject of debate. Adipose cells arise from the recruitment of specific multipotent stem cells/progenitors named adipose tissue-derived stromal cells. Recent studies have highlighted the existence of a variety of those cells being able to differentiate into white, brown or brown-like/beige adipocytes. After commitment to the adipocyte lineage, progenitors undergo large changes in the expression of many genes involved in cell cycle arrest, lipid accumulation and secretory functions. Early nutrition can affect these processes during fetal and perinatal periods and can also influence or pre-determinate later growth of adipose tissue. How these changes may be related to adipose tissue functional maturity around birth and can influence newborn survival is discussed. Altogether, a better knowledge of fetal and postnatal adipose tissue development is important for various aspects of animal production, including neonatal survival, postnatal growth efficiency and health.     

Distinction of white,beige and brown adipocytes derived from mesenchymal stem cells

Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.     

Long non-coding RNAs regulation in adipogenesis and lipid metabolism: Emerging insights in obesity

Obesity is a widespread health problem that brings about various adipose tissue dysfunctions. The balance of energy storage and energy expenditure is critical for normal fat accumulation and lipid metabolism. Therefore, understanding the molecular basis of adipogenesis and thermogenesis is essential to maintain adipose development and lipid homeostasis. Increasing evidence demonstrated that lncRNAs (long non-coding RNAs), a class of non-protein coding RNAs of >200 nucleotides in length, are identified as key regulators in obesity-related biological processes through diverse regulatory mechanisms. In this review, we concentrate on recent and relevant studies on the roles of lncRNAs in regulation of white adipogenesis, brown adipocyte differentiation and lipid metabolism. In addition, the diagnostic and therapeutic potential of lncRNAs is highlighted, and that will make recommendations for the future application of lncRNAs in the treatment of obesity.     

食欲素神经肽在应激过程中的作用

食欲素因其在调节能量代谢、睡眠和唤醒等生理功能中的作用而备受关注.近年来研究逐渐发现,食欲素参与应激和奖赏过程的调节,特别是其在药物成瘾过程中的作用是目前的研究热点.主要介绍食欲素系统与应激相关系统之间的神经联系,阐述了其在应激相关的生理、神经内分泌与行为反应中的作用.并进一步介绍了食欲素系统在应激诱发药物成瘾复吸过程中的作用.食欲素对应激反应的调控作用具有相对特异性,受应激的种类、其他应激相关神经递质系统及食欲素神经元的投射通路等多种因素影响.     

Orexins (hypocretins) and adrenal function.

The recently discovered neuropeptides orexin A and B regulate feeding behavior, neuroendocrine and autonomic functions, and sleep-wakefulness by central mechanisms. The expression of orexins and orexin receptors in various peripheral organs and the presence of orexin A in blood indicate the existence of a peripheral orexin system. In rat and human adrenal glands, both OX (1) and OX (2) receptor subtypes have been described with a predominant expression of OX (2) receptors in the adrenal cortex. In male rats, adrenocortical OX (2) receptors are much higher expressed than in female rats. Various experimental data demonstrate a stimulatory effect of orexins on the secretion of adrenocortical steroids, mainly on glucocorticoids. Some results also suggest the regulation of catecholamine synthesis and release by orexins. Whether the gender-dependent expression of adrenocortical OX (2) receptors has functional correlates awaits future clarification. As plasma orexin appears to rise during hunger and hypoglycemia, orexins may link adrenal functions with energy homeostasis.     

Appetite and energy balance signals from adipocytes

Interest in the biology of white adipose tissue has risen markedly with the recent surge in obesity and its associated disorders. The tissue is no longer viewed simply as a vehicle for lipid storage; instead, it is recognized as a major endocrine and secretory organ. White adipocytes release a multiplicity of protein hormones, signals and factors, termed adipokines, with an extensive range of physiological actions. Foremost among these various adipokines is the cytokine-like hormone, leptin, which is synthesized predominantly in white fat. Leptin plays a critical role in the control of appetite and energy balance, with mutations in the genes encoding the hormone or its receptor leading to profound obesity in both rodents and man. Leptin regulates appetite primarily through an interaction with hypothalamic neuroendocrine pathways, inhibiting orexigenic peptides such as neuropeptide Y and orexin A, and stimulating anorexigenic peptides such as proopiomelanocortin. White fat also secretes several putative appetite-related adipokines, which include interleukin-6 and adiponectin, but whether these are indeed significant signals in the regulation of food intake has not been established. Through leptin and the other adipokines it is evident that adipose tissue communicates extensively with other organs and plays a pervasive role in metabolic homeostasis.     

Re-examination of the putative roles of insulin and prolactin in the regulation of lipid deposition and lipogenesis in vivo in mammary gland and white and brown adipose tissue of lactating rats and litter-removed rats.

1. The effects of various treatments to alter either plasma prolactin (bromocryptine administration or removal of litter) or the metabolic activity of the mammary gland (unilateral or complete teat sealing) on the disposal of oral [14C]lipid between 14CO2 production and [14C]lipid accumulation in tissues of lactating rats were studied. In addition, the rates of lipogenesis in vivo were measured in mammary gland, brown and white adipose tissue and liver. 2. Bromocryptine administration lowered plasma prolactin, but did not alter [14C]lipid accumulation in mammary gland or in white and brown adipose tissue. 3. In contrast, complete sealing of teats results in no change in plasma prolactin, but a 90% decrease in [14C]lipid accumulation in mammary gland and a 4-fold increase in white and brown adipose tissue. The rate of lipogenesis in mammary gland was decreased by 95%, but there was no change in the rate in white and brown adipose tissue. Unilateral sealing of teats resulted in a decrease in [14C]lipid accumulation in white adipose tissue. 4. Removal of the litter for 24 h (low prolactin) produced a similar pattern to complete teat sealing, except that there was a 6-fold increase in lipogenesis in white adipose tissue. Re-suckling for 5 h increased plasma prolactin, but did not alter the response seen in litter-removed lactating rats. 5. Changes in lipoprotein lipase activity and in plasma insulin paralleled the reciprocal changes in [14C]lipid accumulation in white and brown adipose tissue and in mammary gland. 6. It is concluded that the plasma insulin is more important than prolactin in regulating lipid deposition in adipose tissue during lactation, and that any effects of prolactin must be indirect.     

Orexin is required for brown adipose tissue development, differentiation, and function

Orexin (OX) neuropeptides stimulate feeding and arousal. Deficiency of orexin is implicated in narcolepsy, a disease associated with obesity, paradoxically in the face of reduced food intake. Here, we show that obesity in orexin-null mice is associated with impaired brown adipose tissue (BAT) thermogenesis. Failure of thermogenesis in OX-null mice is due to inability of brown preadipocytes to differentiate. The differentiation defect in OX-null neonates is circumvented by OX injections to OX-null dams. In?vitro, OX, triggers the full differentiation program in mesenchymal progenitor stem cells, embryonic fibroblasts and brown preadipocytes via p38 mitogen activated protein (MAP) kinase and bone morphogenetic protein receptor-1a (BMPR1A)-dependent Smad1/5 signaling. Our study suggests that obesity associated with OX depletion is linked to brown-fat hypoactivity, which leads to dampening of energy expenditure. Thus, orexin plays an integral role in adaptive thermogenesis and body weight regulation via effects on BAT differentiation and function.