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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-induced suppression of plasma fatty acid concentrationPlasma fatty acid concentration during the 3h intravenous glucose tolerance test (IVGTT) in LOW-Si (white square □) and NORM-Si (black square ■). Values are mean ± SE. * Significant difference in Area under the curve (AUC) between the groups, P = 0.02.
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Figure 3: Insulin-induced suppression of plasma fatty acid concentrationPlasma fatty acid concentration during the 3h intravenous glucose tolerance test (IVGTT) in LOW-Si (white square □) and NORM-Si (black square ■). Values are mean ± SE. * Significant difference in Area under the curve (AUC) between the groups, P = 0.02.

Mentions: In conjunction with higher insulin sensitivity, fatty acid Rd was nearly 30% lower in NORM-Sivs. LOW-Si (Figure 2; P<0.02). Because we measured fatty acid kinetics under steady-state conditions, fatty acid Rd was equivalent to the rate of fatty acid appearance into the systemic circulation. Therefore, not only is fatty acid uptake lower in NORM-Si vs. LOW-Si, but fatty acid mobilization from adipose tissue was lower as well. Despite the lower rates of fatty acid mobilization and uptake in NORM-Sivs. LOWSi, resting whole-body fatty acid oxidation was not different between groups (3.7 ± 0.2 vs. 3.5 ± 0.2 μmol/kg/min, respectively). Interestingly, fatty acid uptake was reasonably well matched to the rate of fatty acid oxidation in NORM-Si (3.8 ± 0.5 vs. 3.7±0.2 umol/kg/min, respectively), but in LOW-Si the rate of fatty acid uptake exceeded fatty acid oxidation by nearly 50% (5.2 ± 0.4 vs. 3.5 ± 0.2 umol/kg/min, respectively). However, this disparity between fatty acid uptake and fat oxidation in LOW-Si did not translate to a measureable difference in IMTG content, which was similar between groups (63.7 ± 6.7 vs. 68.3 ± 12.7 μmol/g dry weight for NORM- Si and LOW- Si, respectively). In addition to the lower rate of fatty acid uptake in the overnight fasted state in NORM-Si compared with LOW-Si, plasma fatty acid concentration during the IVGTT was also significantly lower in NORM-Sivs. LOW-Si in response to insulin during the IVGTT (AUC: 29±10 vs. 47±15 mM•min, respectively, P=0.02; Figure 3)


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-induced suppression of plasma fatty acid concentrationPlasma fatty acid concentration during the 3h intravenous glucose tolerance test (IVGTT) in LOW-Si (white square □) and NORM-Si (black square ■). Values are mean ± SE. * Significant difference in Area under the curve (AUC) between the groups, P = 0.02.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Insulin-induced suppression of plasma fatty acid concentrationPlasma fatty acid concentration during the 3h intravenous glucose tolerance test (IVGTT) in LOW-Si (white square □) and NORM-Si (black square ■). Values are mean ± SE. * Significant difference in Area under the curve (AUC) between the groups, P = 0.02.
Mentions: In conjunction with higher insulin sensitivity, fatty acid Rd was nearly 30% lower in NORM-Sivs. LOW-Si (Figure 2; P<0.02). Because we measured fatty acid kinetics under steady-state conditions, fatty acid Rd was equivalent to the rate of fatty acid appearance into the systemic circulation. Therefore, not only is fatty acid uptake lower in NORM-Si vs. LOW-Si, but fatty acid mobilization from adipose tissue was lower as well. Despite the lower rates of fatty acid mobilization and uptake in NORM-Sivs. LOWSi, resting whole-body fatty acid oxidation was not different between groups (3.7 ± 0.2 vs. 3.5 ± 0.2 μmol/kg/min, respectively). Interestingly, fatty acid uptake was reasonably well matched to the rate of fatty acid oxidation in NORM-Si (3.8 ± 0.5 vs. 3.7±0.2 umol/kg/min, respectively), but in LOW-Si the rate of fatty acid uptake exceeded fatty acid oxidation by nearly 50% (5.2 ± 0.4 vs. 3.5 ± 0.2 umol/kg/min, respectively). However, this disparity between fatty acid uptake and fat oxidation in LOW-Si did not translate to a measureable difference in IMTG content, which was similar between groups (63.7 ± 6.7 vs. 68.3 ± 12.7 μmol/g dry weight for NORM- Si and LOW- Si, respectively). In addition to the lower rate of fatty acid uptake in the overnight fasted state in NORM-Si compared with LOW-Si, plasma fatty acid concentration during the IVGTT was also significantly lower in NORM-Sivs. LOW-Si in response to insulin during the IVGTT (AUC: 29±10 vs. 47±15 mM•min, respectively, P=0.02; Figure 3)

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