Fig. 1: Obesity is associated with altered phosphocreatine/creatine metabolism in human WAT.

a, Polar metabolites in subcutaneous WAT of obese (n = 13) and non-obese (NO, n = 13) subjects (cohort 1) highlighting metabolites in the phosphocreatine/creatine pathway (green dots). Data are represented in a volcano plot with fold changes (log₂) and adjusted P values (negative (neg.) log₁₀). Statistics were calculated by Welch’s two-sample t-test followed by false discovery rate (FDR) correction for multiple comparisons (q value), according to standard procedures from Metabolon. b, Expression of genes encoding proteins in the phosphocreatine/creatine pathway in subcutaneous WAT of obese (n = 30) and non-obese (n = 26) women (cohort 2). Data are represented in a volcano plot with fold changes (log₂) and adjusted P values (neg. log₁₀) calculated using Limma (linear models for microarray and RNA-seq analysis). c, Western blot analysis of CK-B in subcutaneous WAT of obese (n = 4) and non-obese (n = 5) subjects. Lamin A/C was used as a loading control. *P = 0.036 by Student’s two-sided t-test. d, Representative immunofluorescence microphotographs of subcutaneous WAT from obese (n = 3) and non-obese (n = 3) subjects. Sections were stained with Lens culiniaris agglutinin (Lectin) and antibodies targeting CK-B. Scale bar, 50 μm. e, Creatine kinase activity was measured in total subcutaneous WAT (n = 4 from obese and n = 4 non-obese subjects) as well as isolated mature adipocytes (n = 5 from obese and n = 7 non-obese subjects). As illustrated in the upper panel, the creatine kinase activity measured in this assay represents the reverse reaction after addition of ADP where ATP is generated from phosphocreatine. Lower CK-B activity is expected to result in attenuated ATP levels. *P = 0.05; **P = 0.003 by Student’s two-sided t-test. f, Overview of the phosphocreatine/creatine pathway highlighting the alterations in human subcutaneous WAT linked to obesity. Data are represented as fold changes obese versus non-obese (log₂). *Significant. In c and e, data are shown as mean ± s.e.m. CK-B, cytokine B; MA, mature adipocytes.

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