Brown and beige adipose tissues: phenotype and metabolic potential in mice and men

Chechi, Kanta; Lichtenbelt, Wouter D. van Marken; Richard, Denis

doi:10.1152/japplphysiol.00021.2017

Cited by 38 publications

(45 citation statements)

References 180 publications

(274 reference statements)

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“…This indicates that oxylipins in humans do not per se lack the variability observed in murine tissues but fail to sharply distribute into the categories BAT and WAT. The lack of discrimination of human supraclavicular BAT and WAT oxylipin patterns are in line with the observation that human supraclavicular BAT does not resemble the characteristics of classical BAT in conventional laboratory mice but rather displays a brite phenotype (7,21). Indeed, brite adipose tissue obtained from mice housed at 5 • C for 1 week and human supraclavicular BAT were both characterized by increased UCP1 expression compared to WAT (Supplementary Figure 2 and Figure 1A).…”

Section: The Global Oxylipin Profile Is a Surrogate Marker For The Absupporting

confidence: 80%

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

et al. 2020

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Metabolites of omega-6 and omega-3 polyunsaturated fatty acids are important signaling molecules implicated in the control of adipogenesis and energy balance regulation. Some of these metabolites belonging to the group of oxylipins have been associated with non-shivering thermogenesis in mice mediated by brown or brite adipose tissue. We aimed to identify novel molecules with thermogenic potential and to clarify the relevance of these findings in a translational context. Therefore, we characterized and compared the oxylipin profiles of murine and human adipose tissues with different abundance of brown or brite adipocytes. A broad panel of 36 fatty acid metabolites was quantified in brown and white adipose tissues of C57BL/6J mice acclimatized to different ambient temperatures and in biopsies of human supraclavicular brown and white adipose tissue. The oxylipin profile of murine brite adipose tissue was not distinguishable from white adipose tissue, suggesting that adipose tissue browning in vivo is not associated with major changes in the oxylipin metabolism. Human brown and white adipose tissue also exhibited similar metabolite profiles. This is in line with previous studies proposing human brown adipose tissue to resemble the nature of murine brite adipose tissue representing a heterogeneous mixture of brite and white adipocytes. Although the global oxylipin profile served as a marker for the abundance of thermogenic adipocytes in bona fide brown but not white adipose tissue, we identified 5-HETE and 5,6-EET as individual compounds consistently associated with the abundance of brown or brite adipocytes in human BAT and murine brite fat. Further studies need to establish whether these candidates are mere markers or functional effectors of thermogenic capacity.

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Section: The Global Oxylipin Profile Is a Surrogate Marker For The Absupporting

confidence: 80%

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

et al. 2020

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“…In rodent models of obesity, the activation of BAT and UCP1-positive beige adipocytes in white adipose tissue (WAT) by cold exposure and sympathomimetics (i.e. β3-agonists) can attenuate or reverse obesity, diabetes and atherosclerosis, thus eliciting beneficial effects on metabolic health [1]. One factor which could influence these outcomes is that animals are typically housed at temperatures well below their thermoneutral zone (which for a rodent is c. 28°C) [2].…”

Section: Introductionmentioning

confidence: 99%

Cold exposure drives weight gain and adiposity following chronic suppression of brown adipose tissue

Aldiss

Lewis

Lupini

et al. 2019

Preprint

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Background and aim:Rodents are commonly housed below thermoneutrality and this exposure to 'cold' (i.e. 20°C) activates thermogenic brown (BAT) and beiging of white adipose tissue. Here, we examined whether a standard housing temperature (i.e. 20°C, a reduction in temperature of ~8°C) or YM-178, a highly-selective β 3-adrenoreceptor agonist, in obese animals raised at thermoneutrality, would impact differently on classical BAT or subcutaneous inguinal (IWAT) beige depots. Methods: Eighteen weanling Sprague-Dawley rats were housed at thermoneutrality (28°C) and fed a high-fat diet. At 12 weeks, 6 animals were randomised to either standard housing temperature (20°C, n=6) or to β 3-AR agonist administration (28°C+β3, 0.75mg/kg/d, n=6) for 4 weeks. Metabolic assessment was undertaken during the final 48h, followed by interscapular, perivascular BAT and IWAT sampling for the analysis of thermogenic genes and the proteome. Results: Exposure to 20°C increased weight gain, BAT and IWAT mass. Proteomic analysis of BAT revealed novel pathways associated with cold-induced weight gain (i.e. histone deacetylation, glycosaminoglycan degradation and glycosphingolipid biosynthesis) whilst β 3adrenoreceptor agonism impacted on proteins involved in skeletal muscle contraction and cell differentiation. IWAT of cold-exposed animals exhibited an enrichment of proteins involved NAD+ binding, plus retinol and tyrosine metabolic pathways whilst β 3-AR agonism downregulated ribosomal and upregulated acute phase response proteins. Conclusion: Following diet-induced obesity at thermoneutrality, exposure to 20°C promotes subcutaneous fat deposition in order to reduce heat loss and defend body temperature. In contrast, chronic administration of β 3-AR agonist has minimal metabolic-related effects on adipose tissue.

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“…In addition to classical brown adipose tissue (BAT) depots, pockets of UCP1-positive, multilocular adipocytes have also been described within white adipose tissue (WAT) from rodents following cold exposure, [2][3][4] treatment with a beta 3-adrenergic agonist, 5 or exercise training. 6 These adipocytes are commonly referred to as beige, brite (from brown in white), inducible, or recruitable, reviewed in Chechi et al 7 and seem to result from the transdifferentiation of previously unilocular, white adipocytes 4,5 and from the de novo differentiation of precursor cells. 8 It has been proposed that beige adipocytes can derive from a distinct precursor and display a gene expression pattern different from that of brown adipocytes.…”

Section: Introductionmentioning

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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Brown and beige adipose tissues: phenotype and metabolic potential in mice and men

Cited by 38 publications

References 180 publications

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

Cold exposure drives weight gain and adiposity following chronic suppression of brown adipose tissue

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

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