Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men

Abstract

Higher plasma leucine, isoleucine and valine (BCAA) concentrations are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention. Fasting plasma BCAAs were quantified in an OW (n = 26; BMI 32.4 ± 3 kg/m²; mean age 44 ± 9 y) and a normal-weight (NW) group (n = 26; BMI 24 ± 3.1 kg/m²; mean age 32 ± 12.3 y). Ten of the OW group (BMI 32.2 ± 4 kg/m²; 46 ± 8 y) then underwent 6-weeks of VLCD (600-800 kcal/day). Fasting plasma BCAA (gas chromatography-mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were higher in OW individuals (sum leucine/isoleucine/valine: 457 ± 85 µM) compared to NW control individuals (365 ± 78 µM, p < 0.001). Despite significant weight loss (baseline 103.9 ± 12.3 to 93 ± 9.6 kg and BMI 32.2 ± 4 to 28.9 ± 3.6 kg/m²), no changes were observed in BCAAs after 6-weeks of VLCD. Moreover, although VLCD resulted in a significant reduction in HOMA-IR (baseline 1.19 ± 0.62 to 0.51 ± 0.21 post-VLCD; p < 0.001), Pearson's r revealed no relationships between BCAA and HOMA-IR, either before (leucine R²: 2.49e-005, p = 0.98; isoleucine R²: 1.211-e006, p = 0.9; valine R²: 0.004, p = 0.85) or after VLCD (leucine R²: 0.003, p = 0.86; isoleucine R²: 0.006, p = 0.82; valine R²: 0.002, p = 0.65). Plasma BCAA are higher in OW compared to NW individuals. However, while 6-weeks VLCD reduced body weight and IR in OW individuals, this was not associated with reductions in BCAA. This suggests that studies demonstrating links between BCAA and insulin resistance in OW individuals, are complex and are not normalised by simply losing weight.

Figure 1

Comparison of individual BCAA’s and sum BCAA of OW (n = 26; mean BMI 32.2 ± 2.9 kg/m²) volunteers to NW, age-matched controls (n = 26; mean BMI 25.4 ± 3 kg/m²). There was a significant increase in total BCAA (D) in OW individuals compared to NW. The differences were driven primarily by isoleucine (B) and valine (C). Leucine (A) however remained unchanged.

Figure 2

Baseline and post-VLCD comparisons of fasting plasma BCAA, and BCKA (n = 10). There were no differences in individual (A–C) or sum (D) BCAAs following 6-weeks VLCD. Similarly, there were no differences in individual (E–G) or sum (H) BCKA concentrations following VLCD.

Figure 3

HOMA-IR (A) of individuals with obesity pre and post VLCD (A, P = 0.01) and correlations of HOMA-IR to individual and sum BCAA at baseline and post-VLCD (B–E). The baseline association between HOMA-IR and BCAA across a broader age and BMI range and mixed genders (F) with a greater N = 58 are displayed. The association between HOMA IR to individual BCKA (G–I) and total BCKA (J) are also displayed.