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CD8+ T cells in beige adipogenesis and energy homeostasis
Maria Moysidou, … , Triantafyllos Chavakis, Katia P. Karalis
Maria Moysidou, … , Triantafyllos Chavakis, Katia P. Karalis
Published March 8, 2018
Citation Information: JCI Insight. 2018;3(5):e95456. https://doi.org/10.1172/jci.insight.95456.
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Research Article Metabolism

CD8+ T cells in beige adipogenesis and energy homeostasis

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Abstract

Although accumulation of lymphocytes in the white adipose tissue (WAT) in obesity is linked to insulin resistance, it remains unclear whether lymphocytes also participate in the regulation of energy homeostasis in the WAT. Here, we demonstrate enhanced energy dissipation in Rag1–/– mice, increased catecholaminergic input to subcutaneous WAT, and significant beige adipogenesis. Adoptive transfer experiments demonstrated that CD8+ T cell deficiency accounts for the enhanced beige adipogenesis in Rag1–/– mice. Consistently, we identified that CD8–/– mice also presented with enhanced beige adipogenesis. The inhibitory effect of CD8+ T cells on beige adipogenesis was reversed by blockade of IFN-γ. All together, our findings identify an effect of CD8+ T cells in regulating energy dissipation in lean WAT, mediated by IFN-γ modulation of the abundance of resident immune cells and of local catecholaminergic activity. Our results provide a plausible explanation for the clinical signs of metabolic dysfunction in diseases characterized by altered CD8+ T cell abundance and suggest targeting of CD8+ T cells as a promising therapeutic approach for obesity and other diseases with altered energy homeostasis.

Authors

Maria Moysidou, Sevasti Karaliota, Elisavet Kodela, Maria Salagianni, Yassemi Koutmani, Antonia Katsouda, Konstantia Kodella, Panagiotis Tsakanikas, Styliani Ourailidou, Evangelos Andreakos, Nikolaos Kostomitsopoulos, Dimitris Skokos, Antonios Chatzigeorgiou, Kyoung-Jin Chung, Stefan Bornstein, Mark W. Sleeman, Triantafyllos Chavakis, Katia P. Karalis

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Figure 1

Beige tissue formation in the scWAT is increased in lymphocyte-deficient mice.

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Beige tissue formation in the scWAT is increased in lymphocyte-deficient...
(A–D) Assessment of metabolic behavior using indirect calorimetry, including energy expenditure adjusted to body weight (A), food intake (B), total activity (C), and respiratory exchange ratio (RER) (D). n = 7 per group. (E) Representative H&E-stained images of the scWAT depot of age- and weight-matched Rag1–/– and WT mice. Scale bar: 100 μm. (F) Gene expression analysis of thermogenic and adrenergic receptors. Data are shown as mean expression normalized to actin ± SEM. (G) Absolute weight of scWAT in age- and weight-matched WT and Rag1–/– mice. The data shown are derived from 1 representative of 3 independent experiments. (H) Gene expression analysis of Ucp1 and Cidea in WT and Rag1–/– mice to assess the effect of thermoneutrality, simulated by housing at 30°C for 20 days. Data are shown as mean expression normalized to actin ± SEM. (I) Representative H&E-stained images in the above groups. Scale bar: 100 μm. Data shown are derived from 1 representative of 2 independent experiments. Data are presented as mean ± SEM. n ≥ 4 per group (E–I). *P < 0.05, **P < 0.01, ***P < 0.001, Student’s t test.

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