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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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Correlational analyses for insulin sensitivity with fatty acid uptake and inflammatory markers in skeletal muscle(A) Correlation between insulin sensitivity index (Si) and fatty acid uptake. (B) Correlation between Si and IκB-α abundance. (C) Correlation between Si and p-JNK abundance. All correlational analyses were performed using the entire subject cohort (n=21) [LOW-Si (n=7; white square □), NORM- Si (n=8; black square ■) and participants that did not fall into either category (n=6; grey square  ).
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Figure 5: Correlational analyses for insulin sensitivity with fatty acid uptake and inflammatory markers in skeletal muscle(A) Correlation between insulin sensitivity index (Si) and fatty acid uptake. (B) Correlation between Si and IκB-α abundance. (C) Correlation between Si and p-JNK abundance. All correlational analyses were performed using the entire subject cohort (n=21) [LOW-Si (n=7; white square □), NORM- Si (n=8; black square ■) and participants that did not fall into either category (n=6; grey square ).

Mentions: Among the entire participant population (n=21), fatty acid uptake was inversely correlated with Si, (Figure 5A; R2=0.21; p = 0.04), further supporting the notion that those with relatively low fatty acid uptake were the most insulin sensitive. Similarly, skeletal muscle IκB-α content was positively correlated with Si (Figure 5B; R2=0.22; p=0.035) and skeletal muscle p-JNK tended to be inversely correlated with Si (Figure 5C; R² = 0.18; p= 0.06), both suggesting that lower inflammatory pathway activation in skeletal muscle is related to insulin sensitivity in obesity. We found no correlations between IL-6, MCP-1, or TNF-α in relation to fatty acid uptake (IL-6: R2=0.052, p=0.25; MCP-1: R2=0.0004, p=.94; TNF-α: R2=0.002, p=0.90) or Si (IL-6: R2=0.017, p=0.65; MCP-1: R2=0.0003, p=.70; TNF-α: R2=0.072, p=0.31).


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)

Correlational analyses for insulin sensitivity with fatty acid uptake and inflammatory markers in skeletal muscle(A) Correlation between insulin sensitivity index (Si) and fatty acid uptake. (B) Correlation between Si and IκB-α abundance. (C) Correlation between Si and p-JNK abundance. All correlational analyses were performed using the entire subject cohort (n=21) [LOW-Si (n=7; white square □), NORM- Si (n=8; black square ■) and participants that did not fall into either category (n=6; grey square  ).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4216778&req=5

Figure 5: Correlational analyses for insulin sensitivity with fatty acid uptake and inflammatory markers in skeletal muscle(A) Correlation between insulin sensitivity index (Si) and fatty acid uptake. (B) Correlation between Si and IκB-α abundance. (C) Correlation between Si and p-JNK abundance. All correlational analyses were performed using the entire subject cohort (n=21) [LOW-Si (n=7; white square □), NORM- Si (n=8; black square ■) and participants that did not fall into either category (n=6; grey square ).
Mentions: Among the entire participant population (n=21), fatty acid uptake was inversely correlated with Si, (Figure 5A; R2=0.21; p = 0.04), further supporting the notion that those with relatively low fatty acid uptake were the most insulin sensitive. Similarly, skeletal muscle IκB-α content was positively correlated with Si (Figure 5B; R2=0.22; p=0.035) and skeletal muscle p-JNK tended to be inversely correlated with Si (Figure 5C; R² = 0.18; p= 0.06), both suggesting that lower inflammatory pathway activation in skeletal muscle is related to insulin sensitivity in obesity. We found no correlations between IL-6, MCP-1, or TNF-α in relation to fatty acid uptake (IL-6: R2=0.052, p=0.25; MCP-1: R2=0.0004, p=.94; TNF-α: R2=0.002, p=0.90) or Si (IL-6: R2=0.017, p=0.65; MCP-1: R2=0.0003, p=.70; TNF-α: R2=0.072, p=0.31).

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