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Relatively low endogenous fatty acid mobilization and uptake helps preserve insulin sensitivity in obese women.

Van Pelt DW, Newsom SA, Schenk S, Horowitz JF - Int J Obes (Lond) (2014)

Bottom Line: The subset of participants with the lowest S(i) (LOW-S(i); S(i) ⩽ 2.1 (mU/l)(-1) min(-1); n = 7) was compared with the subset of participants with the highest S(i), who exhibited relatively normal insulin sensitivity (NORM-S(i); S(i) ⩾ 3.4 (mU/l)(-1) min(-1); n = 8).Importantly, the greater rate of fatty acid uptake in LOW-S(i) vs NORM-S(i) did not translate to higher rate of fat oxidation (3.5 ± 0.2 vs 3.7 ± 0.2 μmol kg(-1) min(-1)) or to a measureable difference in IMTG content (68.3 ± 12.7 vs 63.7 ± 6.7 μmol g(-1) dry weight).In contrast, LOW-S(i) and NORM-S(i) exhibited no differences in plasma markers of inflammation (TNFα, IL-6 (interleukin-6), MCP-1).

View Article: PubMed Central - PubMed

Affiliation: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USA.

ABSTRACT

Background: Although obesity is commonly linked with metabolic disease risk, some obese adults do not develop metabolic abnormalities, such as insulin resistance.

Objectives: The primary aim of this study was to determine whether alterations in fatty acid mobilization and uptake underlie differences in insulin sensitivity (Si) among a seemingly homogeneous cohort of obese women.

Methods: Insulin sensitivity (frequently sampled intravenous glucose tolerance test), basal fatty acid rate of disappearance from plasma (Rd), resting whole-body fat oxidation, intramyocellular triacylglycerol (IMTG) concentration and markers of skeletal muscle inflammation were measured in 21 obese women. Participants were divided into tertiles based on their S(i). The subset of participants with the lowest S(i) (LOW-S(i); S(i) ⩽ 2.1 (mU/l)(-1) min(-1); n = 7) was compared with the subset of participants with the highest S(i), who exhibited relatively normal insulin sensitivity (NORM-S(i); S(i) ⩾ 3.4 (mU/l)(-1) min(-1); n = 8).

Results: Despite nearly identical physical characteristics in LOW-S(i) vs NORM-S(i) (body mass index: 34 ± 2 vs 34 ± 1 kg m(-2); %body fat: 48 ± 1 vs 47 ± 1%; waist circumference: 104 ± 2 vs 104 ± 2 cm; VO2 max: 2.2 ± 0.2 vs 2.3 ± 0.1 l min(-1)), fatty acid Rd was nearly 30% lower in NORM (P=0.02). Importantly, the greater rate of fatty acid uptake in LOW-S(i) vs NORM-S(i) did not translate to higher rate of fat oxidation (3.5 ± 0.2 vs 3.7 ± 0.2 μmol kg(-1) min(-1)) or to a measureable difference in IMTG content (68.3 ± 12.7 vs 63.7 ± 6.7 μmol g(-1) dry weight). In conjunction with the lower fatty acid Rd in NORM-S(i) vs LOW-S(i), activation of inflammatory pathways known to impair insulin action in skeletal muscle was also lower (lower phosphorylated c-jun N-terminal kinase (JNK) and higher inhibitor of κB (IκB-α) abundance). In contrast, LOW-S(i) and NORM-S(i) exhibited no differences in plasma markers of inflammation (TNFα, IL-6 (interleukin-6), MCP-1).

Conclusion: These findings suggest that obese women who maintain a relatively low rate of endogenous fatty acid uptake may be somewhat 'protected' against the development of insulin resistance potentially by less activation of inflammatory pathways within skeletal muscle.

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Markers of inflammation(A) Total protein abundance of phosphorylated c- Jun N-terminal kinase (p-JNK) (B) Total protein abundance of Inhibitor of NF-κB α (IκB-α). *P < 0.05 for NORM-Sivs. LOW-Si
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Figure 4: Markers of inflammation(A) Total protein abundance of phosphorylated c- Jun N-terminal kinase (p-JNK) (B) Total protein abundance of Inhibitor of NF-κB α (IκB-α). *P < 0.05 for NORM-Sivs. LOW-Si

Mentions: Within skeletal muscle, JNK phosphorylation (p-JNK) was significantly lower in NORM- Si compared with LOW-Si (Figure 4A), suggestive of attenuated inflammatory pathway activation in muscle from NORM-Si participants. This may have been due in part to a lower total JNK protein abundance in NORM-Sivs. LOW-Si (101±10 vs. 149±20 arbitrary units (AU), respectively; p ≤0.05). Skeletal muscle protein abundance of IκB-α tended to be greater in NORM-Si compared with LOW-Si (Figure 4B), but this difference between groups did not quite reach statistical significance (p=0.067). Because IκB-α suppresses activation of the IKK-NFκB inflammatory pathway30, the trend for greater abundance of IκB-α in muscle from NORM-Sivs. LOW-Si is also indicative of reduced inflammation in NORM-Si. In contrast to the differences in markers of inflammation in skeletal muscle, there were no significant differences in fasting plasma concentrations of IL-6 (15.0 ± 8.4 vs. 23.8 ± 10.0 pg/ml), TNF-α (4.3 ±1.0 vs. 7.9 ± 2.2 pg/ml), or MCP- 1 (128.5 ± 12.6 vs. 114.5 ± 32.7 pg/ml) between NORM-Si and LOW-Si, respectively.


Relatively low endogenous fatty acid mobilization and uptake helps preserve insulin sensitivity in obese women.

Van Pelt DW, Newsom SA, Schenk S, Horowitz JF - Int J Obes (Lond) (2014)

Markers of inflammation(A) Total protein abundance of phosphorylated c- Jun N-terminal kinase (p-JNK) (B) Total protein abundance of Inhibitor of NF-κB α (IκB-α). *P < 0.05 for NORM-Sivs. LOW-Si
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4216778&req=5

Figure 4: Markers of inflammation(A) Total protein abundance of phosphorylated c- Jun N-terminal kinase (p-JNK) (B) Total protein abundance of Inhibitor of NF-κB α (IκB-α). *P < 0.05 for NORM-Sivs. LOW-Si
Mentions: Within skeletal muscle, JNK phosphorylation (p-JNK) was significantly lower in NORM- Si compared with LOW-Si (Figure 4A), suggestive of attenuated inflammatory pathway activation in muscle from NORM-Si participants. This may have been due in part to a lower total JNK protein abundance in NORM-Sivs. LOW-Si (101±10 vs. 149±20 arbitrary units (AU), respectively; p ≤0.05). Skeletal muscle protein abundance of IκB-α tended to be greater in NORM-Si compared with LOW-Si (Figure 4B), but this difference between groups did not quite reach statistical significance (p=0.067). Because IκB-α suppresses activation of the IKK-NFκB inflammatory pathway30, the trend for greater abundance of IκB-α in muscle from NORM-Sivs. LOW-Si is also indicative of reduced inflammation in NORM-Si. In contrast to the differences in markers of inflammation in skeletal muscle, there were no significant differences in fasting plasma concentrations of IL-6 (15.0 ± 8.4 vs. 23.8 ± 10.0 pg/ml), TNF-α (4.3 ±1.0 vs. 7.9 ± 2.2 pg/ml), or MCP- 1 (128.5 ± 12.6 vs. 114.5 ± 32.7 pg/ml) between NORM-Si and LOW-Si, respectively.

Bottom Line: The subset of participants with the lowest S(i) (LOW-S(i); S(i) ⩽ 2.1 (mU/l)(-1) min(-1); n = 7) was compared with the subset of participants with the highest S(i), who exhibited relatively normal insulin sensitivity (NORM-S(i); S(i) ⩾ 3.4 (mU/l)(-1) min(-1); n = 8).Importantly, the greater rate of fatty acid uptake in LOW-S(i) vs NORM-S(i) did not translate to higher rate of fat oxidation (3.5 ± 0.2 vs 3.7 ± 0.2 μmol kg(-1) min(-1)) or to a measureable difference in IMTG content (68.3 ± 12.7 vs 63.7 ± 6.7 μmol g(-1) dry weight).In contrast, LOW-S(i) and NORM-S(i) exhibited no differences in plasma markers of inflammation (TNFα, IL-6 (interleukin-6), MCP-1).

View Article: PubMed Central - PubMed

Affiliation: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USA.

ABSTRACT

Background: Although obesity is commonly linked with metabolic disease risk, some obese adults do not develop metabolic abnormalities, such as insulin resistance.

Objectives: The primary aim of this study was to determine whether alterations in fatty acid mobilization and uptake underlie differences in insulin sensitivity (Si) among a seemingly homogeneous cohort of obese women.

Methods: Insulin sensitivity (frequently sampled intravenous glucose tolerance test), basal fatty acid rate of disappearance from plasma (Rd), resting whole-body fat oxidation, intramyocellular triacylglycerol (IMTG) concentration and markers of skeletal muscle inflammation were measured in 21 obese women. Participants were divided into tertiles based on their S(i). The subset of participants with the lowest S(i) (LOW-S(i); S(i) ⩽ 2.1 (mU/l)(-1) min(-1); n = 7) was compared with the subset of participants with the highest S(i), who exhibited relatively normal insulin sensitivity (NORM-S(i); S(i) ⩾ 3.4 (mU/l)(-1) min(-1); n = 8).

Results: Despite nearly identical physical characteristics in LOW-S(i) vs NORM-S(i) (body mass index: 34 ± 2 vs 34 ± 1 kg m(-2); %body fat: 48 ± 1 vs 47 ± 1%; waist circumference: 104 ± 2 vs 104 ± 2 cm; VO2 max: 2.2 ± 0.2 vs 2.3 ± 0.1 l min(-1)), fatty acid Rd was nearly 30% lower in NORM (P=0.02). Importantly, the greater rate of fatty acid uptake in LOW-S(i) vs NORM-S(i) did not translate to higher rate of fat oxidation (3.5 ± 0.2 vs 3.7 ± 0.2 μmol kg(-1) min(-1)) or to a measureable difference in IMTG content (68.3 ± 12.7 vs 63.7 ± 6.7 μmol g(-1) dry weight). In conjunction with the lower fatty acid Rd in NORM-S(i) vs LOW-S(i), activation of inflammatory pathways known to impair insulin action in skeletal muscle was also lower (lower phosphorylated c-jun N-terminal kinase (JNK) and higher inhibitor of κB (IκB-α) abundance). In contrast, LOW-S(i) and NORM-S(i) exhibited no differences in plasma markers of inflammation (TNFα, IL-6 (interleukin-6), MCP-1).

Conclusion: These findings suggest that obese women who maintain a relatively low rate of endogenous fatty acid uptake may be somewhat 'protected' against the development of insulin resistance potentially by less activation of inflammatory pathways within skeletal muscle.

Show MeSH
Related in: MedlinePlus