Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages

Yu, Haidong; Dilbaz, Sedat; Coßmann, Jonas; Hoang, Anh Cuong; Diedrich, Victoria; Herwig, Annika; Harauma, Akiko; Hoshi, Yukino; Moriguchi, Takahiko; Landgraf, Kathrin; Körner, Antje; Lucas, Christina; Brodesser, Susanne; Balogh, Lajos; Thuróczy, Julianna; Karemore, Gopal; Kuefner, Michael; Park, Edwards A.; Rapp, Christine M.; Travers, Jeffrey B.; Röszer, Tamás

doi:10.1172/jci125646

Cited by 95 publications

(186 citation statements)

References 106 publications

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“…In mammals, alkylglycerols (AKGs) can be produced and secreted from lactating mammary gland cells (14). In this issue of the JCI, Yu and Dilbaz et al establish that AKGs are highly enriched in breast milk at micromolar levels and make the observation that breastfed human infants display increased levels of UCP1, with abundant multilocular adipocytes enriched in mitochondria, consistent with the widespread presence of BeAT in inguinal AT (iAT) (15). These attributes are not present in iAT in infants who are not at all or only rarely breastfed.…”

Section: Alkylglycerols Maintain Beat In Infant Atmentioning

confidence: 96%

Critical lipids link breastfeeding to healthy adipose tissue in infancy and adulthood

Gliniak

Scherer²

2019

Journal of Clinical Investigation

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Section: Alkylglycerols Maintain Beat In Infant Atmentioning

confidence: 96%

Critical lipids link breastfeeding to healthy adipose tissue in infancy and adulthood

Gliniak

Scherer²

2019

Journal of Clinical Investigation

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“…Alkylglycerol in breast milk maintains the beige adipose tissue in infants and children below 5 years of age and impedes the transformation of beige adipose tissue into WAT. Alkylglycerol induces the beige adipocyte phenotype in the adipose tissues in a macrophage-dependent manner, and its function in beige adipose tissue development is mediated by the platelet-activating factor via IL-6/STAT3 signaling activation 46 .…”

Section: Lipid As a Regulator Of Thermogenic Fat Activationmentioning

confidence: 99%

Clinical Application Potential of Small Molecules that Induce Brown Adipose Tissue Thermogenesis by Improving Fat Metabolism

Dass

Tsai

et al. 2020

Cell Transplant

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Mammalian fat comprises white and brown adipose tissue (WAT and BAT, respectively). WAT stores energy, whereas BAT is used for thermogenesis. In recent years, the incidence of obesity and its associated disorders have increased tremendously. Considering the thermogenic capacity and decreased levels of BAT with increasing age, BAT can be used as a suitable therapeutic target for the treatment of obesity and diabetes. In several studies, using positron emission tomography and computed tomography images, adult humans have been shown to have functional BAT in interscapular fat. Results of these basic research studies on BAT have shed light on the new components of transcriptional regulation and the role of hormones in stimulating BAT growth and differentiation. In this review article, we have summarized the thermogenic regulators identified in the past decades by focusing on peroxisome proliferator-activated receptor gamma/uncoupling protein 1 activators, branched-chain amino acids, fatty acids (lipokine), and adenosine monophosphate-activated protein kinase mediators. We have also presented the progress of a few ongoing clinical trials aimed at the treatment of obesity and its associated metabolic disorders. The main purpose of this review was to provide a comprehensive introduction to the latest knowledge of the representative thermogenic regulators for the treatment of obesity. The fat combustion capacity of BAT may have great potential and can be considered as a suitable target for the therapeutic application of drugs from bench-to-bed treatment of obesity and the associated diseases.

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“…Which route of WAT browning is triggered by immune cells remains to be characterized. In addition to cold stimulation, physiological process such as burn injury [43,44], exercise [45][46][47], cancer cachexia [48][49][50][51], lactation in females [52,53], and various circulating factors (hormones and metabolites) [45,[54][55][56][57][58][59][60][61][62][63] also affect beige adipocyte formation, although the involvement of the sympathetic nervous system and the contribution of de novo beige adipogenesis or transdifferentiation (or both) in these settings have not be thoroughly determined. Beige adipocytes can be found in most, if not all, subcutaneous fat depots especially under cold adaptation [64].…”

Section: Figurementioning

confidence: 99%

Towards a Better Understanding of Beige Adipocyte Plasticity

Paulo

Wang

2019

Cells

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Beige adipocytes are defined as Ucp1 + , multilocular adipocytes within white adipose tissue (WAT) that are capable of thermogenesis, the process of heat generation. In both mouse models and humans, the increase of beige adipocyte population, also called WAT browning, is associated with certain metabolic benefits, such as reduced obesity and increased insulin sensitivity. In this review, we summarize the current knowledge regarding WAT browning, with a special focus on the beige adipocyte plasticity, collectively referring to a bidirectional transition between thermogenic active and latent states in response to environmental changes. We further exploit the utility of a unique beige adipocyte ablation system to interrogate anti-obesity effect of beige adipocytes in vivo.It has been well established that activity of beige adipocytes is dominantly regulated by the sympathetic nervous system, induced by the cold or just the feeling of cold ( Figure 1) [6][7][8]. Chemical denervation with 6-hydroxydopamina, prior to 3-week-old age or prior to cold exposure, impairs beige adipocyte formation, indicating the importance of sympathetic nerves during WAT browning [21]. Previous studies on anatomical positioning of sympathetic nerves in the subcutaneous inguinal white adipose tissue (iWAT), for example, by staining the tyrosine hydrolase + (Th + ) sympathetic nerves in fixed tissues [22,23], lack spatial and temporal precision [21,24,25]. Th + -sympathetic nerves and beige adipocytes are not distributed evenly across iWAT [22], suggesting that anatomic positioning of sympathetic nerves may also contribute to beige adipocyte formation. However, the actions of sympathetic nerves, the engagement of neurotransmitters, and their receptors at the contact sites of the sympathetic nerve and receiving cell in live mice are most unknown, and functional relevance of sympathetic nerve neurotransmission in beige adipocyte plasticity, especially during the postnatal period, is not fully elucidated yet.Cells 2019, 8, 1552 2 of 16 environment, but their appearances are also negatively correlated with aging and obesity, suggesting a potential role of beige adipocytes in regulating energy homeostasis. Beige Adipocyte Formation: Different PlayersIt has been well established that activity of beige adipocytes is dominantly regulated by the sympathetic nervous system, induced by the cold or just the feeling of cold (Figure 1) [6][7][8]. Chemical denervation with 6-hydroxydopamina, prior to 3-week-old age or prior to cold exposure, impairs beige adipocyte formation, indicating the importance of sympathetic nerves during WAT browning [21]. Previous studies on anatomical positioning of sympathetic nerves in the subcutaneous inguinal white adipose tissue (iWAT), for example, by staining the tyrosine hydrolase + (Th + ) sympathetic nerves in fixed tissues [22,23], lack spatial and temporal precision [21,24,25]. Th + -sympathetic nerves and beige adipocytes are not distributed evenly across iWAT [22], suggesting that anatomic positioning of sympatheti...

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Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages

Cited by 95 publications

References 106 publications

Critical lipids link breastfeeding to healthy adipose tissue in infancy and adulthood

Critical lipids link breastfeeding to healthy adipose tissue in infancy and adulthood

Clinical Application Potential of Small Molecules that Induce Brown Adipose Tissue Thermogenesis by Improving Fat Metabolism

Towards a Better Understanding of Beige Adipocyte Plasticity

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