TitleRelatively low endogenous fatty acid mobilization and uptake helps preserve insulin sensitivity in obese women.
Publication TypeJournal Article
Year of Publication2015
AuthorsVan Pelt, DW, Newsom, SA, Schenk, S, Horowitz, JF
JournalInt J Obes (Lond)
Date Published01/2015
KeywordsAbsorptiometry, Photon, Adult, Blood Glucose, Body Composition, Fatty Acids, Female, Humans, Inflammation, Insulin, Insulin Resistance, Michigan, Muscle, Skeletal, Obesity

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.

Alternate JournalInt J Obes (Lond)
PubMed ID24785103
PubMed Central IDPMC4216778
Grant ListUL1 TR000433 / TR / NCATS NIH HHS / United States
R01 DK077966 / DK / NIDDK NIH HHS / United States
P30 DK089503 / DK / NIDDK NIH HHS / United States
P30DK089503 / DK / NIDDK NIH HHS / United States
P30DK020572 / DK / NIDDK NIH HHS / United States
2UL1TR000433 / TR / NCATS NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
R01DK077966 / DK / NIDDK NIH HHS / United States