Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue.

Bianco, Antonio C.; Silva, J E

doi:10.1172/jci112798

Cited by 317 publications

(200 citation statements)

References 26 publications

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“…The thyroid hormone T 3 plays an important role in the activation of brown adipocytes, and thyroidectomized rats exhibit impaired BAT activation and thermoregulation in response to cold 38, 3940 and human multipotent adipose‐derived stem cells under adipogenic conditions 41.…”

Section: Resultsmentioning

confidence: 99%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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BackgroundIntramuscular fatty infiltration is generally associated with the accumulation of white adipocytes in skeletal muscle and unfavourable metabolic outcomes. It is, however, still unclear whether intramuscular adipocytes could also acquire a brown‐like phenotype. Here, we detected intramuscular expression of brown adipocyte markers during fatty infiltration in an obesity‐resistant mouse strain and extensively compared the potential of two different stem cell populations residing in skeletal muscle to differentiate into brown‐like adipocytes.MethodsFatty infiltration was induced using intramuscular glycerol or cardiotoxin injection in the tibialis anterior muscles of young or aged 129S6/SvEvTac (Sv/129) mice or interleukin‐6 (IL‐6) knockout mice, and the expression of general and brown adipocyte markers was assessed after 4 weeks. Fibro/adipogenic progenitors (FAPs) and myogenic progenitors were prospectively isolated using fluorescence‐activated cell sorting from skeletal muscle of male and female C57Bl6/6J and Sv/129 mice, and monoclonal and polyclonal cultures were treated with brown adipogenic medium. Additionally, FAPs were differentiated with medium supplemented or not with triiodothyronine.ResultsAlthough skeletal muscle expression of uncoupling protein 1 (Ucp1) was barely detectable in uninjected tibialis anterior muscle, it was drastically induced following intramuscular adipogenesis in Sv/129 mice and further increased in response to beta 3‐adrenergic stimulation. Intramuscular Ucp1 expression did not depend on IL‐6 and was preserved in aged skeletal muscle. Myogenic progenitors did not form adipocytes neither in polyclonal nor monoclonal cultures. Fibro/adipogenic progenitors, on the other hand, readily differentiated into brown‐like, UCP1+ adipocytes. Uncoupling protein 1 expression in differentiated FAPs was regulated by genetic background, sex, and triiodothyronine treatment independently of adipogenic differentiation levels.ConclusionsIntramuscular adipogenesis is associated with increased Ucp1 expression in skeletal muscle from obesity‐resistant mice. Fibro/adipogenic progenitors provide a likely source for intramuscular adipocytes expressing UCP1 under control of both genetic and hormonal factors. Therefore, FAPs constitute a possible target for therapies aiming at the browning of intramuscular adipose tissue and the metabolic improvement of skeletal muscle affected by fatty infiltration.

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Section: Resultsmentioning

confidence: 99%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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“…For example, it is only during chronic hypothermia (i.e. following 48 h at 4°C) when body temperature declines to 29°C that a clear association between restoration of UCP content of BAT and nuclear T3 saturation exists (Bianco & Silva, 1987). Similarly the magnitude of decline in UCP mRNA following a 48 h period of food deprivation is directly linked to ambient and colonic temperature (Champigny & Ricquier, 1990).…”

Section: Discussionmentioning

confidence: 99%

Adipose Tissue Development During Early Postnatal Life in Ewe-Reared Lambs

Clarke¹,

BUSS²,

JUNIPER³

et al. 1997

Exp. Physiol.

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SUMMARYThis study examines the precise time course that brown adipose tissue (BAT) takes to adopt the characteristics of white adipose tissue in postnatal lambs. Perirenal adipose tissue was sampled from ewe-reared lambs within 1 h of birth and at 1, 2, 4, 7, 14, 21 and 30 days of age and analysed for the amount of mRNA for uncoupling protein (UCP), the amount and activity of UCP, and protein, mitochondrial protein and lipid content. This was combined with measurements of colonic temperature and jugular venous plasma concentrations of thyroid hormones and insulinlike growth factor-I (IGF-1). Over the first 4-7 days of age, large quantities of UCP mRNA were associated with a peak in plasma triiodothyronine concentration at 2 days of age followed by a maximal amount and activity of UCP at 4 days and a basal colonic temperature of 39 3°C. Between 7 and 30 days there was a large increase in lipid deposition as the amount and activity of UCP and the amount of UCP mRNA declined to basal values and colonic temperature was maintained at 40 'C. A significant positive relationship between perirenal adipose tissue lipid content and plasma IGF-1 concentration was observed throughout the study period. It is concluded that ovine adipose tissue maturation occurs in two distinct phases over the first month of life. The precise time scale of this process could be regulated in part by the lamb's body temperature which determines whether adipose tissue is required for heat production (i.e. BAT) or as an endogenous energy source (i.e. white adipose tissue).

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“…cAMP-induced D2 activation in BAT leads to rapid saturation of TR with locally generated T 3 and induction of T 3 -responsive genes and the activity of T 3 -responsive enzymes, without affecting circulating thyroid hormone levels (66,86,233,237,(267)(268)(269)271). This is also observed in animal models of transgenic Dio2 expression in the heart (273,274).…”

Section: [F1] Thyrotoxicosis In Animalsmentioning

confidence: 97%

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Bianco

Anderson

Forrest

et al. 2014

Thyroid

173

106

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Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue.

Cited by 317 publications

References 26 publications

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Adipose Tissue Development During Early Postnatal Life in Ewe-Reared Lambs

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

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