Fig. 1: Adipose glutaminolysis is increased in obesity-induced insulin resistance.
From: Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health
a, Correlations between amino acid levels in plasma and insulin sensitivity (left), amino acid levels in WAT and insulin sensitivity (middle) and between amino acid levels in plasma (n = 53) and WAT (n = 26) (right) in cohort 1. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp expressed as glucose disposal rate corrected for mean plasma insulin levels at steady state (M/I). Associations were calculated using Spearman’s rank correlation. b, The plasma (n = 53) (left) and WAT (n = 26) (right) glutamine-to-glutamate (gln to glu) ratios in cohort 1 comparing women living without (w/o) or with obesity (BMI ≥ 30 kg m−2). Groups were compared using Student’s t-test. c, The correlation between WAT glutamine-to-glutamate ratios and waist-to-hip ratio (left) or fat cell volume (right) in cohort 1 (n = 26). Pearson’s correlation coefficients are shown. d, Expression of genes encoding glutamine–glutamate (gln–glu) metabolizing proteins measured by qPCR in isolated fat cells from cohort 2. Results are displayed according to biological pathways and compared for people living w/o (n = 12) or with (n = 16) obesity. Groups were compared using Student’s t-test or the Mann–Whitney U-test, depending on the distribution. e, Protein levels of GLS and GLUL in subcutaneous white adipocytes from participants living w/o (n = 4) or with (n = 3) obesity (cohort 2). Proteins derived from the same samples were loaded on two different gels. f, GLS activity in subcutaneous adipocytes from participants living w/o (n = 7) or with (n = 8) obesity in cohort 2. Groups were compared using Student’s t-test. g, Correlations between indicated clinical and adipocyte parameters and GLUL or GLS expression in bulk transcriptomic data of subcutaneous WAT from cohort 3 (n = 56). All correlations were significant (P < 0.05), circle sizes are proportional to the Pearson’s correlation coefficient and the colour indicates positive (pos.) (green) or negative (neg.) (purple) associations. Data in b, d and f show mean ± s.e.m. Relevant P values are shown. asp-asn, aspartate to asparagine conversion; energy exp., energy expenditure by indirect calorimetry corrected for body weight (kcal kg−1 day−1); GMP, guanosine monophosphate; ins-stim. lipog., log10 maximal insulin-stimulated lipogenesis in isolated mature fat cells.
