Introduction and Objective: Acute elevation of non-esterified fatty acids (NEFA) can induce peripheral insulin resistance and impair glucose uptake in muscle. Rodent studies have shown that elevation of NEFA through a high-fat diet impairs brain glucose uptake, and prior observational studies by our group have reported that higher NEFA levels correlate with lower brain glucose. Here, we test whether acute elevations in circulating NEFA in lean individuals can induce impairment in brain glucose uptake.Methods: Lean, healthy adults underwent either intravenous infusion of saline or Intralipid 20% at 60 mL/hr for 4 hours followed by hyperglycemic clamp (target 180 mg/dL) and 1H MRS scanning to measure changes in brain glucose on two separate occasions. Saline/Intralipid infusion was continued throughout the hyperglycemic clamp and MRS scanning. Brain glucose was measured by 1H MRS at 3 Tesla.Results: Five lean, healthy adults completed the study (age 24.8 ± 6.8 years, BMI 22.9 ± 1.2 kg/m2, A1c 5.0 ± 0.2%). Four hours of Intralipid infusion led to a ~2.5-fold elevation in circulating NEFA at the beginning of the hyperglycemic clamp (Intralipid 1.4 ± 0.5 vs. saline 0.59 ± 0.08 mmol/L, p=0.04). NEFA levels differed between treatments during the hyperglycemic clamp (p<0.01, two-way mixed ANOVA). Between saline vs. Intralipid infusion, there were no differences in plasma glucose (183 ± 7 vs. 181 ± 7 mg/dL, p=0.31), plasma insulin (41 ± 15 vs. 44 ± 17 mU/L, p=0.64), glucose infusion rate (4.4 ± 1.2 vs. 4.8 ± 1.6 mg/kg*min, p=0.44), or change in brain glucose (0.26 ± 0.03 vs. 0.28 ± 0.07 mmol/L, p=0.67) during steady state hyperglycemia (average 60-120 minutes of clamp).Conclusion: Despite significantly higher NEFA levels, there were no differences in measures of insulin sensitivity following Intralipid. We conclude that elevation of circulating NEFA for hours (to levels higher than normal physiologic conditions) in the presence of hyperglycemia and absence of insulin resistance has no impact on brain glucose uptake.
B.C. Matson: None. W. Chang: None. J.J. Palmiotto: None. D.L. Rothman: None. R. Belfort De Aguiar: None. G.F. Mason: Consultant; Merck & Co., Inc. Research Support; Pfizer Inc. Consultant; Leal Therapeutics. J.J. Hwang: None.
National Institutes of Health (R01DK123227)
Source link
Leave a Reply