Brown and Beige Adipose Tissue and Aging

Zoico, Elena; Rubele, Sofia; De, Annamaria; Nori, Nicole; Mazzali, Gloria; Fantin, Francesco; Rossi, Andrea P.; Zamboni, Mauro

doi:10.3389/fendo.2019.00368

Cited by 141 publications

(134 citation statements)

References 90 publications

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“…Titan mice also display higher levels of intra-abdominal fat, which correlates with hyperinsulinemia, whitening of BAT, and fat cells presence in the pancreas. BAT whitening is strongly linked to obesity (Kotzbeck et al, 2018) and becomes more prevalent during aging in both humans and rodents (Zoico et al, 2019). As mice age, small lipid droplets normally observed in brown adipocytes coalesce into a single vacuole (Brayton et al, 2012), as observed in Titan mice.…”

Section: Discussionmentioning

confidence: 99%

Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse

Mueller-Eigner

Sanz-Moreno

de-Diego

et al. 2020

Preprint

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Metabolic syndrome is widespread and negatively impacts healthy longevity but takes years to study in mammalian models, delaying translational applications. To address this, we characterized the unique polygenic "Titan" mouse (110 grams average) with a healthy lifespan of only 4 months that was generated by 45 years of breeding selection. Titan mice displayed increased plasma leptin, insulin, IL-6 and fasting triglycerides. Also, pancreatic fat cell accumulation and thymic medullary hyperplasia were detected in Titan animals. Liver transcriptome and proteome analysis demonstrated alterations in lipid metabolism, the methionine cycle, and cytochrome P450 regulation in Titan mice. Late dietary intervention in Titan mice reduced fat content and improved expression of genes involved in lipid synthesis and cytochrome P450 detoxification, altering the abundance of metabolites, including malonyl-CoA and dimethylglycine. Strikingly, late dietary intervention at 3 months of age almost doubled the healthy lifespan of Titan mice. This powerful model of metabolic disorders, systemic inflammation, and early aging will enable to provide uniquely rapid results for translational intervention.

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Section: Discussionmentioning

confidence: 99%

Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse

Mueller-Eigner

Sanz-Moreno

de-Diego

et al. 2020

Preprint

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“…The UCP1-mediated proton leak is thereby specific to BAT thermogenesis: a diminished proton gradient permits an increased rate in the series of exothermic reactions generating the protein gradient, from the TCA cycle through the ETC, and increases the rate of collisions between protons and other molecules, generating substantial heat (24). Mitochondrial dysfunction and age-related hormonal changes that regulate UCP1 expression may also explain why BAT activation correlates negatively with age (25).…”

Section: Cellular Thermogenesismentioning

confidence: 99%

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Chen

Brychta

Sater

et al. 2020

Journal of Biological Chemistry

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The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through β-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.

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“…Since cold acclimation is able to recruit the BAT in obese patients, BAT activation may also improve obesity-associated insulin resistance and hyperglycemia [18]. The activity of adult brown and beige fat decreases with aging [19][20][21] and may contribute to the progression of chronic metabolic diseases. Taken together, these findings suggest that activating and recruiting brown and beige fat would be beneficial to improving overall metabolic health.…”

Section: Thermogenesis and Adipose Tissuementioning

confidence: 99%

Thermogenesis in Adipose Tissue Activated by Thyroid Hormone

Yau

Yen

2020

IJMS

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Thermogenesis is the production of heat that occurs in all warm-blooded animals. During cold exposure, there is obligatory thermogenesis derived from body metabolism as well as adaptive thermogenesis through shivering and non-shivering mechanisms. The latter mainly occurs in brown adipose tissue (BAT) and muscle; however, white adipose tissue (WAT) also can undergo browning via adrenergic stimulation to acquire thermogenic potential. Thyroid hormone (TH) also exerts profound effects on thermoregulation, as decreased body temperature and increased body temperature occur during hypothyroidism and hyperthyroidism, respectively. We have termed the TH-mediated thermogenesis under thermoneutral conditions “activated” thermogenesis. TH acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein (Ucp1) to generate heat. TH acts centrally to activate the BAT and browning through the sympathetic nervous system. However, recent studies also show that TH acts peripherally on the BAT to directly stimulate Ucp1 expression and thermogenesis through an autophagy-dependent mechanism. Additionally, THs can exert Ucp1-independent effects on thermogenesis, most likely through activation of exothermic metabolic pathways. This review summarizes thermogenic effects of THs on adipose tissues.

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Brown and Beige Adipose Tissue and Aging

Cited by 141 publications

References 90 publications

Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse

Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Thermogenesis in Adipose Tissue Activated by Thyroid Hormone

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