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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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Insulin sensitivity(A) Insulin sensitivity index (Si) measured the morning after an overnight fast in all subjects (n=21). Subjects were ordered from highest to lowest Si, and stratified into tertiles to identify a low insulin sensitivity cohort (LOW- Si; Si ≤2.1 (mU/L)−1·min−1; n=7) and a normal insulin sensitivity cohort (NORM-Si; Si ≥3.4 (mU/L)−1·min−1) (B) mean Si in NORM-Si and LOW-Si cohorts. *P < 0.000001 vs. NORM- Si
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Figure 1: Insulin sensitivity(A) Insulin sensitivity index (Si) measured the morning after an overnight fast in all subjects (n=21). Subjects were ordered from highest to lowest Si, and stratified into tertiles to identify a low insulin sensitivity cohort (LOW- Si; Si ≤2.1 (mU/L)−1·min−1; n=7) and a normal insulin sensitivity cohort (NORM-Si; Si ≥3.4 (mU/L)−1·min−1) (B) mean Si in NORM-Si and LOW-Si cohorts. *P < 0.000001 vs. NORM- Si

Mentions: As designed, the participant pool was largely homogeneous in terms of BMI, adiposity, waist circumference, and cardiorespiratory fitness (Table 1); however, Si varied widely among the 21 participants (Figure 1), ranging from 4.8 to 0.8 (mU/L)−1·min−1. As noted in Figure 1A, participants with Si in the lowest one-third of the overall participant pool (≤2.1 (mU/L)−1·min−1) were grouped into the “low” insulin sensitive cohort (LOW-Si; n=7), and those in the highest one-third (≥3.4 (mU/L)−1·min−1) were grouped into the “normal” insulin sensitivity cohort (NORM-Si; n=8). The term “normal” was used to define the Si of the most insulin sensitive participants because these values were very similar to those previously reported by our laboratory and others for lean, healthy adults20,25,28,29. As designed, the difference in Si between NORM- Si and LOW- Si was highly significant (Figure 1B; P<0.000001); but importantly, these groups were very well matched for BMI, adiposity, waist circumference, and cardiorespiratory fitness (Table 1). In addition, fasting plasma glucose and insulin concentrations were similar in NORM-Si and LOW-Si (Table 1; p=0.47, p=0.28, respectively). In order to compare groups with distinct differences in insulin sensitivity, primary comparisons did not include participants with Si values between 2.1 and 3.4 (mU/L)−1·min−1 (grey bars in Figure 1). The participants with intermediate Si were included in correlation analyses, which incorporated the entire participant pool. The racial profile within our groups were as follows: NORM-Si - 2 African American and 6 Caucasian women; LOW-Si –1 African American, 1 Asian, 1 Hispanic/Latino and 4 Caucasian women; Intermediate-Si – 2 African American and 4 Caucasian women.


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)

Insulin sensitivity(A) Insulin sensitivity index (Si) measured the morning after an overnight fast in all subjects (n=21). Subjects were ordered from highest to lowest Si, and stratified into tertiles to identify a low insulin sensitivity cohort (LOW- Si; Si ≤2.1 (mU/L)−1·min−1; n=7) and a normal insulin sensitivity cohort (NORM-Si; Si ≥3.4 (mU/L)−1·min−1) (B) mean Si in NORM-Si and LOW-Si cohorts. *P < 0.000001 vs. NORM- Si
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4216778&req=5

Figure 1: Insulin sensitivity(A) Insulin sensitivity index (Si) measured the morning after an overnight fast in all subjects (n=21). Subjects were ordered from highest to lowest Si, and stratified into tertiles to identify a low insulin sensitivity cohort (LOW- Si; Si ≤2.1 (mU/L)−1·min−1; n=7) and a normal insulin sensitivity cohort (NORM-Si; Si ≥3.4 (mU/L)−1·min−1) (B) mean Si in NORM-Si and LOW-Si cohorts. *P < 0.000001 vs. NORM- Si
Mentions: As designed, the participant pool was largely homogeneous in terms of BMI, adiposity, waist circumference, and cardiorespiratory fitness (Table 1); however, Si varied widely among the 21 participants (Figure 1), ranging from 4.8 to 0.8 (mU/L)−1·min−1. As noted in Figure 1A, participants with Si in the lowest one-third of the overall participant pool (≤2.1 (mU/L)−1·min−1) were grouped into the “low” insulin sensitive cohort (LOW-Si; n=7), and those in the highest one-third (≥3.4 (mU/L)−1·min−1) were grouped into the “normal” insulin sensitivity cohort (NORM-Si; n=8). The term “normal” was used to define the Si of the most insulin sensitive participants because these values were very similar to those previously reported by our laboratory and others for lean, healthy adults20,25,28,29. As designed, the difference in Si between NORM- Si and LOW- Si was highly significant (Figure 1B; P<0.000001); but importantly, these groups were very well matched for BMI, adiposity, waist circumference, and cardiorespiratory fitness (Table 1). In addition, fasting plasma glucose and insulin concentrations were similar in NORM-Si and LOW-Si (Table 1; p=0.47, p=0.28, respectively). In order to compare groups with distinct differences in insulin sensitivity, primary comparisons did not include participants with Si values between 2.1 and 3.4 (mU/L)−1·min−1 (grey bars in Figure 1). The participants with intermediate Si were included in correlation analyses, which incorporated the entire participant pool. The racial profile within our groups were as follows: NORM-Si - 2 African American and 6 Caucasian women; LOW-Si –1 African American, 1 Asian, 1 Hispanic/Latino and 4 Caucasian women; Intermediate-Si – 2 African American and 4 Caucasian women.

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