Greater dietary fat oxidation in obese compared with lean men: an adaptive mechanism to prevent liver fat accumulation?

Abstract

Liver fat represents a balance between input, secretion, and oxidation of fatty acids. As humans spend the majority of a 24-h period in a postprandial state, dietary fatty acids make an important contribution to liver fat metabolism. We compared hepatic fatty acid partitioning in healthy lean (n = 9) and abdominally obese (n = 10) males over 24 h. Volunteers received three mixed meals adjusted for basal metabolic rate. U-13C-labeled fatty acids were incorporated into the meals, and [2H2]palmitate was infused intravenously to distinguish between sources of fatty acids incorporated into VLDL-TG. Immunoaffinity chromatography was used to isolate VLDL-TG of hepatic origin. Liver and whole body fatty acid oxidation was assessed by isotopic enrichment of 3-hydoxybutyrate and breath CO2. We found a similar contribution of dietary fatty acids to VLDL-TG in the two groups over 24 h. The contribution of fatty acids from splanchnic sources was higher (P < 0.05) in the abdominally obese group. Ketogenesis occurred to a significantly greater extent in abdominally obese compared with lean males, largely due to lessened downregulation of postprandial ketogenesis (P < 0.001). The appearance of 13C in breath CO2 was also greater (P < 0.001) in abdominally obese compared with lean men. Hepatic elongation and desaturation of palmitic acid were higher (P < 0.05) in abdominally obese than in lean males. Oxidation of dietary fatty acids and hepatic desaturation and elongation of palmitic acid occurred to a greater extent in abdominally obese men. These alterations may represent further pathways for redirection of fatty acids into export from the liver or oxidation to prevent liver fat accumulation.

Fig. 1.

Overview of hepatic fatty acid partitioning using stable isotope-labeled fatty acids to trace the fate of dietary fatty acids (using U-¹³C-labeled fatty acids) and endogenous fatty acids (using [²H₂]palmitate). *Where stable isotope enrichment was measured; †breath CO₂ representing dietary fatty acid oxidation. FA, fatty acid; NEFA, nonesterified fatty acids; DNL; de novo lipogenesis; TG; triglyceride; 3-OHB, 3-hydroxybutyrate; VLDL, very low-density lipoprotein.

Fig. 2.

Concentrations of TG in plasma (A; AUC P = 0.007, iAUC P = NS) and in S_f20–400 lipoprotein fraction (B; AUC P = 0.022, iAUC P = 0.001) in lean (●) and abdominally obese (○) males (n = 9 and 10 respectively). Data are presented as means ± SE.

Fig. 3.

Concentrations of dietary [U-¹³C]linoleate (●), [U-¹³C]oleate (○), and [U-¹³C]palmitate (▾) in plasma TG (A and B), plasma NEFAs (C and D), and VLDL-TG (E and F). Lean subjects (n = 9), left; abdominally obese subjects (n = 10), right. Data are presented as means ± SE.

Fig. 4.

Plasma NEFA [²H₂]16:0/16:0 tracer-to-tracee ratio (TTR; A, P = NS), VLDL-TG isotopic SCD index (B, P = 0.008), and isotopic elongation index (C, P = 0.039) in lean (●) and abdominally obese (○) males (n = 9 and 10, respectively). For explanation of indexes, see text. Data are presented as means ± SE.

Fig. 5.

Plasma 3-OHB concentrations (A, P = 0.007) and enrichment of plasma 3-OHB (B, P = 0.035) and breath CO₂ (C, P < 0.001) with ¹³C from dietary fatty acids in lean (●) and abdominally obese (○) males (n = 9 and 10, respectively). Data are presented as means ± SE.