A heart–adipose tissue connection in the regulation of energy metabolism

Collins, Sheila

doi:10.1038/nrendo.2013.234

Cited by 122 publications

(127 citation statements)

References 79 publications

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“…There have been reports demonstrating significant roles of heart-derived natriuretic peptides (NP), wellknown regulators of fluid and hemodynamic homeostasis, in BAT recruitment [53]. NP enhances whole-body EE, probably due to an up-regulation of UCP1 in BAT and induction of beige/brite adipocytes.…”

Section: Conflicts Of Interestmentioning

confidence: 99%

Human brown adipose tissue: regulation and anti-obesity potential [Review]

Saito

2014

Endocr J

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Abstract. Brown adipose tissue (BAT) is the site of sympathetically activated adaptive thermognenesis during cold exposure and after hyperphagia, thereby controlling whole-body energy expenditure (EE) and body fat. Radionuclide imaging studies have demonstrated that adult humans have metabolically active BAT composed of mainly beige/brite adipocytes, recently identified brown-like adipocytes. The inverse relationship between the BAT activity and body fatness suggests that BAT is, because of its energy dissipating activity, protective against body fat accumulation in humans as it is in small rodents. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruits BAT in parallel with increased EE and decreased body fat. In addition to the sympathetic nervous system, several endocrine factors are also shown to recruit BAT. Thus, BAT is a promising therapeutic target for combating human obesity and related metabolic disorders.Key words: Beige/brite adipocyte, Body fat, Brown adipose tissue, Energy expenditure, ObesityIn mAmmAls, there are two types of adipose tissue, white and brown adipose tissues, which are quite different in the physiological functions. White adipose tissue (WAT) is the site of energy storage, while brown adipose tissue (BAT) is specialized for non-shivering thermogenesis to dissipate energy as heat. In small rodents, BAT has long been recognized as the major site of sympathetically activated adaptive thermogenesis during cold exposure and probably after spontaneous overfeeding. This specific thermogenic organ has currently gathered increasing attention as a therapeutic target for combating human obesity and related metabolic disorders [1][2][3]. This is because of several remarkable advancements in BAT research over the last few years. First, being against the conventional view that human BAT is functional only in neonates, recent radionuclide imaging studies have revealed the existence of a considerable amount of BAT in adult humans [4][5][6][7]. There are now piles of evidence indicating BAT as a significant regulatory site of wholebody energy expenditure (EE) and body fatness in not only small rodents but also humans. Second, studies in rodent models revealed two types of themogenic adipocytes arising from distinct developmental lineages: "classical" brown adipocytes" and "beige/brite" adipocytes [8, 9]. Several key transcriptional regulators and signaling molecules in the developmental pathways of brown and beige/brite adipocytes have been identified [10]. Third, while the sympathetic nervous system is a central regulator of BAT function, several endocrine/ paracrine molecules were also identified as significant activators/recruiters of BAT [11]. Lastly, some studies investigating the effects of BAT transplantation suggest possible roles of BAT in the regulation of glucose and lipid metabolism through some body fat-independent mechanisms [12, 13]. Based on these findings, this review summarizes the regulatory mechan...

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Section: Conflicts Of Interestmentioning

confidence: 99%

Human brown adipose tissue: regulation and anti-obesity potential [Review]

Saito

2014

Endocr J

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“…Likewise, beige adipocytes have also attracted much attention as an antiobesity target, due to their inducible nature and relevance to adult humans (1,2,4,5,8,15). Cold exposure, sympathetic transmission, thyroid hormone, and cardiac natriuretic peptides induce UCP1-mediated thermogenesis via stimulation of the β-adrenergic receptormediated (β-AR-mediated) cAMP/PKA pathway, which primarily activates the transcriptional coactivator PPARγ coactivator 1-α (PGC1-α) (5,16). PGC1-α promotes respiration, thermogenesis, and mitochondrial biogenesis by stimulating several transcription factors and coactivators (4,17,18).…”

Section: Introductionmentioning

confidence: 99%

Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

Zhu

Ghoshal

Rodrigues

et al. 2016

Journal of Clinical Investigation

156

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“…Lipolysis is an exquisitely regulated process. Food deprivation initiates lipolysis through the hormonal activation of adipocytes by catecholamines or natriuretic peptides, activation of protein kinases A or G, downstream phosphorylation of multiple proteins of the lipolytic pathway, and release of coactivator proteins such as comparative gene identification-58 (CGI-58) (4,5). These events, in turn, strongly activate ATGL and HSL resulting in efficient TG hydrolysis.…”

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confidence: 99%

Hypophagia and metabolic adaptations in mice with defective ATGL-mediated lipolysis cause resistance to HFD-induced obesity

Schreiber

Hofer

Taschler

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Adipose triglyceride lipase (ATGL) initiates intracellular triglyceride (TG) catabolism. In humans, ATGL deficiency causes neutral lipid storage disease with myopathy (NLSDM) characterized by a systemic TG accumulation. Mice with a genetic deletion of ATGL (AKO) also accumulate TG in many tissues. However, neither NLSDM patients nor AKO mice are exceedingly obese. This phenotype is unexpected considering the importance of the enzyme for TG catabolism in white adipose tissue (WAT). In this study, we identified the counteracting mechanisms that prevent excessive obesity in the absence of ATGL. We used "healthy" AKO mice expressing ATGL exclusively in cardiomyocytes (AKO/cTg) to circumvent the cardiomyopathy and premature lethality observed in AKO mice. AKO/cTg mice were protected from high-fat diet (HFD)-induced obesity despite complete ATGL deficiency in WAT and normal adipocyte differentiation. AKO/cTg mice were highly insulin sensitive under hyperinsulinemic-euglycemic clamp conditions, eliminating insulin insensitivity as a possible protective mechanism. Instead, reduced food intake and altered signaling by peroxisome proliferator-activated receptor-gamma (PPAR-γ) and sterol regulatory element binding protein-1c in WAT accounted for the phenotype. These adaptations led to reduced lipid synthesis and storage in WAT of HFD-fed AKO/cTg mice. Treatment with the PPAR-γ agonist rosiglitazone reversed the phenotype. These results argue for the existence of an adaptive interdependence between lipolysis and lipid synthesis. Pharmacological inhibition of ATGL may prove useful to prevent HFDinduced obesity and insulin resistance.E ssentially all organisms face the problem of continuous energy demand in an environment of irregular food supply. To overcome this dilemma, metazoan organisms developed special storage depots for substrates that are used for energy production. In vertebrates, by far the most efficient energy reservoir is adipose tissue (1). This highly expandable organ is able to store all major nutritional components (fat, carbohydrates, and proteins) as triglycerides (TGs). Adipose tissue mass and TG content depend on the balance of anabolic and catabolic pathways. Lipid storage in response to nutrient supply involves the generation of adipocytes (adipogenesis), the induction of fatty acid (FA) synthesis from glucose and amino acids (de novo lipogenesis), and the synthesis of TGs (lipid synthesis). These processes are activated by a complex transcriptional network involving CCAAT/ enhancer-binding proteins (C/EBPs), sterol regulatory enhancer binding proteins (SREBPs), and the heterodimer of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and retinoid-X receptor (RXR) (2, 3).The opposing metabolic pathway of TG catabolism (lipolysis) requires activation of enzymes called lipases. Adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase (MGL) hydrolyze all three ester bonds of TGs in a stepwise manner to yield FAs and glycerol (4). Lipolysis is an exquisitely regulated proce...

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A heart–adipose tissue connection in the regulation of energy metabolism

Cited by 122 publications

References 79 publications

Human brown adipose tissue: regulation and anti-obesity potential [Review]

Human brown adipose tissue: regulation and anti-obesity potential [Review]

Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

Hypophagia and metabolic adaptations in mice with defective ATGL-mediated lipolysis cause resistance to HFD-induced obesity

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