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

Hodson L, McQuaid SE, Humphreys SM, Milne R, Fielding BA, Frayn KN, Karpe F - Am. J. Physiol. Endocrinol. Metab. (2010)

Bottom Line: We found a similar contribution of dietary fatty acids to VLDL-TG in the two groups over 24 h.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).These alterations may represent further pathways for redirection of fatty acids into export from the liver or oxidation to prevent liver fat accumulation.

View Article: PubMed Central - PubMed

Affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. leanne.hodson@oxlip.ox.ac.uk

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.

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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.
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Figure 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.

Mentions: The [2H2]palmitate TTRs in the plasma NEFA pool were similar in lean and abdominally obese males over the course of the study (Fig. 4A). We used the isotopic desaturation index ([2H2]16:1 n-7/[2H2]16:0) of VLDL-TG as a marker of hepatic SCD activity. Over the 24 h, both groups had similar concentrations of [2H2]16:0 in VLDL-TG, but the abdominally obese men had a higher (P = 0.003) concentration of [2H2]16:1 n-7 than the lean males. The isotopic desaturation index over the 24-h period was higher in the abdominally obese than in the lean men (AUC 0.27 ± 0.07 vs. 0.04 ± 0.02, P = 0.008;Fig. 4B). Similarly, we used the isotopic elongation index ([2H2]18:0/[2H2]16:0) of VLDL-TG as a marker of hepatic Elovl 6 activity. The elongation of [2H2]16:0 was consistently higher in abdominally obese than in the lean males over the 24-h period (AUC 0.08 ± 0.02 vs. 0.02 ± 0.01, P = 0.004, respectively; Fig. 4C).


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

Hodson L, McQuaid SE, Humphreys SM, Milne R, Fielding BA, Frayn KN, Karpe F - Am. J. Physiol. Endocrinol. Metab. (2010)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957864&req=5

Figure 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.
Mentions: The [2H2]palmitate TTRs in the plasma NEFA pool were similar in lean and abdominally obese males over the course of the study (Fig. 4A). We used the isotopic desaturation index ([2H2]16:1 n-7/[2H2]16:0) of VLDL-TG as a marker of hepatic SCD activity. Over the 24 h, both groups had similar concentrations of [2H2]16:0 in VLDL-TG, but the abdominally obese men had a higher (P = 0.003) concentration of [2H2]16:1 n-7 than the lean males. The isotopic desaturation index over the 24-h period was higher in the abdominally obese than in the lean men (AUC 0.27 ± 0.07 vs. 0.04 ± 0.02, P = 0.008;Fig. 4B). Similarly, we used the isotopic elongation index ([2H2]18:0/[2H2]16:0) of VLDL-TG as a marker of hepatic Elovl 6 activity. The elongation of [2H2]16:0 was consistently higher in abdominally obese than in the lean males over the 24-h period (AUC 0.08 ± 0.02 vs. 0.02 ± 0.01, P = 0.004, respectively; Fig. 4C).

Bottom Line: We found a similar contribution of dietary fatty acids to VLDL-TG in the two groups over 24 h.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).These alterations may represent further pathways for redirection of fatty acids into export from the liver or oxidation to prevent liver fat accumulation.

View Article: PubMed Central - PubMed

Affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. leanne.hodson@oxlip.ox.ac.uk

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.

Show MeSH
Related in: MedlinePlus