Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling

Fabbiano, Salvatore; Suárez-Zamorano, Nicolas; Rigo, Dorothée; Veyrat-Durebex, Christelle; Dokic, Ana Stevanovic; Colin, Didier; Trajkovski, Mirko

doi:10.1016/j.cmet.2016.07.023

Cited by 254 publications

(224 citation statements)

References 44 publications

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“…Several interventions have been described, which can reverse the phenotype of reduced mitochondrial function in WAT in obesity, the two most prominent examples being caloric restriction and treatment using PPARγ agonists [60]. Interestingly, this can be related to BAT as well, since PPARγ is considered one of the main regulators of BAT function as well as formation and since it was recently shown that caloric restriction induces BAT mass and functionality [61]. Taken together, it is tempting to speculate that the induction of a brown fat phenotype by the abovementioned interventions, which would result in an increased mitochondrial functionality, could be the reason for the observed beneficial effects on aging and metabolism.…”

Section: Impact Of Age On Mitochondria: Biogenesis Function Bioenermentioning

confidence: 99%

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Schosserer

Grillari²,

Wolfrum

et al. 2017

Gerontology

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Aging is a time-related process of functional decline at organelle, cellular, tissue, and organismal level that ultimately limits life. Cellular senescence is a state of permanent growth arrest in response to stress and one of the major drivers of aging and age-related disorders. Senescent cells accumulate with age, and removal of these cells delays age-related disorders in different tissues and prolongs healthy lifespan. One of the most studied aging mechanisms is the accumulation of reactive oxygen species damage in cells, organs, and organisms over time. Elevated oxidative stress is also found in metabolic diseases such as obesity, metabolic syndrome and associated disorders. Moreover, dysregulation of the energy homeostasis is also associated with aging, and many age-related genes also control energy metabolism, with the adipose organ, comprising white, brite, and brown adipocytes, as an important metabolic player in the regulation of whole-body energy homeostasis. This review summarizes transformations in the adipose organ upon aging and cellular senescence and sheds light on the reallocation of fat mass between adipose depots, on the metabolism of white and brown adipose tissue, on the regenerative potential and adipogenic differentiation capacity of preadipocytes, and on alterations in mitochondria and bioenergetics. In conclusion, the aging process is a lifelong, creeping process with gradual decline in (pre-)adipocyte function over time. Thus, slowing down the accumulation of (pre-)adipocyte damage and dysfunction, removal of senescent preadipocytes as well as blocking deleterious compounds of the senescent secretome are protective measures to maintain a lasting state of health at old age.

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Section: Impact Of Age On Mitochondria: Biogenesis Function Bioenermentioning

confidence: 99%

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Schosserer

Grillari²,

Wolfrum

et al. 2017

Gerontology

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“…www.jlr.org Downloaded from eosinophils may be required for the WAT beiging in their models [16,31,73,74,115].…”

Section: Downloaded Frommentioning

confidence: 99%

“…To date, at least 10 primary research articles have examined the role of ILC2s in WAT homeostasis [14,16,31,94,95,112,113,115,117,119]. The initial studies used an RNase glycoprotein extracted from the Helminth egg to elicit weight loss and improve glucose tolerance associated with increased ILC2s, eosinophils, and M2-like macrophages [14].…”

Section: Ilc2s In Wat Type 2 Inflammation: Caveats and Controversiesmentioning

confidence: 99%

“…The presence of beige fat is most notably induced by both acute and prolonged cold exposure, and is increased in humans during colder winter months [15]. Caloric restriction was also shown to induce beiging in obese mice [16], but a recent study indicates this mechanism may not be conserved in humans [17]; or at the very least, that there is greater variability of beiging capacity One of the most surprising discoveries about AT was the accumulation of proinflammatory immune cells in WAT in obesity [23,24]. In the last few decades, it has come to light that the immune system is a key regulator of WAT homeostasis.…”

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confidence: 99%

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Contributions of innate type 2 inflammation to adipose function

Bolus

Hasty

2019

Journal of Lipid Research

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A critical contributor to health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function are all altered in obesity-related disease, white AT is marked by progressive inflammation & adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts continue seeking interventions to mitigate obesity-associated AT inflammation, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g. beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology. prospective analyses of nearly a million adults, showed that obesity can decrease a person's life span up to 10 years [7]. Thus, a better understanding of adipose tissue (AT), the organ that expands the most in size during obesity, should provide solutions to this health concern.When discussing AT, white adipose tissue (WAT) is most commonly considered; however, other types of AT, brown adipose tissue (BAT) and beige AT also exist.Adipocytes in WAT and BAT are generated from unique progenitors. WAT stores excess energy in the form of triglycerides. BAT can store small amounts of triglycerides; however, its primary role is to burn fatty acids to generate heat. Beige fat has brown-like properties but is transiently present in WAT depots (especially subcutaneous) upon beta-adrenergic stimulation. Regulation of all three of these fat depots is critically important for lipid and energy homeostasis.WAT consists of spatially distinct beds: visceral, omental, subcutaneous, perivascular, epicardial, and many others. These depots serve to cushion organs they BAT is localized primarily in subscapular regions in rodents, and was only discovered in adult humans in the past decade [10,11]. BAT has a characteristic brown appearance grossly, and is easily distinguished from WAT. This distinctive color is due to the presence of concentrated mitochondria within each brown adipocyte, accompanied by high iron concentrations required for activation of the electron transport chain during beta-oxidation. High expression of uncoupling protein 1 (UCP-1) causes this beta-oxidation to result in generation of heat rather than ATP (thermogenesis), thus assistin...

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“…UCP1 is a hallmark of BAT, and recent studies have revealed that this protein is induced along with an increase in mitochondrial content in WAT during browning [53]. Moreover, accumulating studies have identified several other dominant transcriptional regulators of brown fat development and function, including PPARγ, PGC-1α, and PRDM16 [54]. PGC-1α is α major cofactor known to play a key role in mitochondrial biogenesis [50].…”

Section: Discussionmentioning

confidence: 99%

Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO) is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. Methods: Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 10⁸ or 2.0 × 10¹⁰ vector genomes) or Control-AAV-EGFP (2.0 × 10⁸ vector genomes) was injected into the third ventricle. After administration, the rats were fed a high-fat diet (HFD) for 9 weeks to induce obesity. Rats fed a chow fat diet were used as normal controls. Results: LKB1 delivery decreased body weight, energy intake, fat mass, and serum lipid levels. LKB1 also improved HFD-induced hepatic fatty degeneration. Interestingly, LKB1 over-expression in the hypothalamus activated the AMPK-POMC neurons-sympathetic nervous system (SNS) axis, which can release epinephrine to promote white fat browning. Conversely, the elevated expression of MC3R/MC4R inhibited food intake. These two factors worked together to inhibit the development of obesity. Conclusions: LKB1 in the hypothalamus may have therapeutic potential for DIO through the activation of the AMPK-POMC neurons-SNS axis.

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Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling

Cited by 254 publications

References 44 publications

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Contributions of innate type 2 inflammation to adipose function

Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis

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