Exercise increases TCA intermediate concentrations during low‐calorie diet independent of insulin resistance among women with obesity

Tricarboxylic acid cycle intermediates (TCAi) have been proposed to act as myokines that influence energy metabolism. We determined if 2‐weeks of low‐calorie diet with interval exercise (LCD + INT) would increase TCAi more than a low‐calorie diet (LCD). Twenty‐three women were randomized to 2‐weeks of LCD ( n = 12, 48.4 ± 2.5 years, 37.8 ± 1.5 kg/m 2 , ~1200 kcal/d) or LCD + INT ( n = 11, 47.6 ± 4.3 years, 37.9 ± 2.3 kg/m 2 ; 60 min/d supervised INT of 3 min 90% & 50% HRpeak). TCAi and amino acids (AA) were measured at 0 min of a 75 g OGTT, while glucose, insulin, and FFA were obtained at 0, 30, 60, 90, 120, and 180 min to assess total area under the curve (tAUC 180min ) and insulin resistance (IR; tAUC 180min of Glucose × Insulin). Fuel use (indirect calorimetry) was also collected at 0, 60, 120, and 180 min as was fitness (VO 2 peak) and body composition (BodPod). Treatments reduced weight ( p < 0.001), fasting RER ( p = 0.01), and IR ( p = 0.03), although LCD + INT increased VO 2 peak ( p = 0.02) and maintained RER tAUC 180min ( p = 0.05) versus LCD. Treatments increased FFA tAUC 180min ( p = 0.005), cis‐aconitate, isocitrate, and succinate ( p ≤ 0.02), as well as reduced phenylalanine and tryptophan, cysteine ( p ≤ 0.005). However, LCD + INT increased malate, citrate, α‐ketoglutarate, and alanine more than LCD ( p ≤ 0.04). Thus, INT enhanced LCD effects on some TCAi in women with obesity independent of IR.