Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice

Karlina, Ruth; Lutter, Dominik; Miok, Viktorian; Fischer, David; Altun, Irem; Schöttl, Theresa; Schorpp, Kenji; Israel, Andreas; Cero, Cheryl; Johnson, James W.; Kapser-Fischer, Ingrid; Böttcher, Anika; Keipert, Susanne; Feuchtinger, Annette; Graf, Elisabeth; Strom, Tim M.; Walch, Axel; Lickert, Heiko; Walzthoeni, Thomas; Heinig, Matthias; Theis, Fabian J.; García‐Cáceres, Cristina; Cypess, Aaron M.; Ussar, Siegfried

doi:10.26508/lsa.202000924

Cited by 17 publications

(12 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A key element of healthy adipose tissue expansion is de novo differentiation of adipocytes rather than storage of fat in already existing adipocytes 4,5 . However, recent data indicate the existence of multiple white [6][7][8][9] and brown 10,11 adipocyte subtypes that originate from distinct precursor populations. Thus, the type of de novo differentiating adipocytes could strongly affect the metabolic response of the organism to weight gain, as lipid storage capacity, as well as adipokine production differs between white adipocyte subtypes [6][7][8][9] .…”

mentioning

confidence: 99%

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

et al. 2021

Self Cite

View full text Add to dashboard Cite

Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.

show abstract

mentioning

confidence: 99%

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whether this could reflect some variation in previously unidentified subtype heterogeneity among adipocytes at embryonic stages, or is due to variation in the differentiation states of cells within a single adipocyte population is not clear. qRT-PCR on Hoxa5 null sBAT revealed no effect on embryonic expression of recently-identified markers for subtypes of adult brown adipocyte ( Karlina et al, 2021 ), including Bin1, Tcf24, Eif5 or P2rx5 (not shown).…”

Section: Resultsmentioning

confidence: 82%

“…However, only high- Ucp1 expressing subtypes were found until a few days after birth ( Song et al, 2020 ), and we did not find significant differences in any subtype markers other than Ucp1 in Hoxa5 null embryos. It would be interesting to determine whether some of the recently discovered heterogeneity among BAT adipoctyes does develop pre-natally ( Song et al, 2020 ; Karlina et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

HOXA5 Participates in Brown Adipose Tissue and Epaxial Skeletal Muscle Patterning and in Brown Adipocyte Differentiation

Holzman

Ryckman

Finkelstein

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Brown adipose tissue (BAT) plays critical thermogenic, metabolic and endocrine roles in mammals, and aberrant BAT function is associated with metabolic disorders including obesity and diabetes. The major BAT depots are clustered at the neck and forelimb levels, and arise largely within the dermomyotome of somites, from a common progenitor with skeletal muscle. However, many aspects of BAT embryonic development are not well understood. Hoxa5 patterns other tissues at the cervical and brachial levels, including skeletal, neural and respiratory structures. Here, we show that Hoxa5 also positively regulates BAT development, while negatively regulating formation of epaxial skeletal muscle. HOXA5 protein is expressed in embryonic preadipocytes and adipocytes as early as embryonic day 12.5. Hoxa5 null mutant embryos and rare, surviving adults show subtly reduced iBAT and sBAT formation, as well as aberrant marker expression, lower adipocyte density and altered lipid droplet morphology. Conversely, the epaxial muscles that arise from a common dermomyotome progenitor are expanded in Hoxa5 mutants. Conditional deletion of Hoxa5 with Myf5/Cre can reproduce both BAT and epaxial muscle phenotypes, indicating that HOXA5 is necessary within Myf5-positive cells for proper BAT and epaxial muscle development. However, recombinase-based lineage tracing shows that Hoxa5 does not act cell-autonomously to repress skeletal muscle fate. Interestingly, Hoxa5-dependent regulation of adipose-associated transcripts is conserved in lung and diaphragm, suggesting a shared molecular role for Hoxa5 in multiple tissues. Together, these findings establish a role for Hoxa5 in embryonic BAT development.

show abstract

“…Expression of Cidea, Prdm16, Tmem26, and Ppargc1a, all markers for brown and beige adipocytes, was increased in scWAT of HDM-exposed HFD-fed mice. 58,59 A potential link between HDM-induced inflammation and increased thermogenic gene expression in scWAT is via the observed increase in IL-13 and IL-4 expression. This could activate eosinophils to secrete IL-4, which acts directly on Pdgfra + precursor cells to increase the proliferation and differentiation of beige/ thermogenic adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of lung inflammation on insulin resistance in humans and mice

Karlina

Flexeder

Musiol

et al. 2022

Allergy

Self Cite

View full text Add to dashboard Cite

Background:The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity. The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis.Methods: Epidemiological data from 2207 adults of the population-based KORA FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were Funding informationThe KORA study was initiated and financed by the Helmholtz Zentrum München-German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Mouse studies were supported by the HMGU Allergy Projects from the Helmholtz Center Munich.intranasally sensitized and challenged with HDM and simultaneously fed with either low-fat or high-fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver, and adipose tissues. Results:We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis, and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1.Conclusions: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation, and hepatosteatosis.

show abstract

Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice

Cited by 17 publications

References 57 publications

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

HOXA5 Participates in Brown Adipose Tissue and Epaxial Skeletal Muscle Patterning and in Brown Adipocyte Differentiation

Differential effects of lung inflammation on insulin resistance in humans and mice

Contact Info

Product

Resources

About