Deficits in brain glucose transport among younger adults with obesity

Abstract

Objective: Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism.

Methods: A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-¹³C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance.

Results: Individuals with obesity demonstrated an ~20% lower ratio of brain glucose uptake to cerebral glucose metabolic rate (T_max/CMR_glucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (V_TCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and T_max/CMR_glucose (r = -0.477; p = 0.045).

Conclusions: We conclude that CMR_glucose is unlikely to differ between groups due to similar V_TCA, and, therefore, the glucose transport T_max is lower in individuals with obesity. These human findings suggest that obesity is associated with reduced cerebral glucose transport capacity even at a young age and in the absence of other cardiometabolic comorbidities, which may have implications for long-term brain function and health.

Figure 1.. Schema of scanning protocol and plasma glucose levels during hyperglycemic clamp.

(A) Schema of scanning protocol. (B) Plasma glucose levels in participants during the hyperglycemic clamp expressed as mean ± SD.

Figure 2.. Representative spectra.

(A) Representative C1 glucose spectra for one lean participant and one participant with obesity following infusion with [1-¹³C] glucose. α and β anomers of glucose are labeled in the C1 position. ppm, parts per million. (B) Representative spectra of glutamine (Gln) and glutamate (Glu) for one lean participant and one participant with obesity following infusion with [1-¹³C] glucose. ppm, parts per million.

Figure 3.. Steady state brain glucose and T_max/CMR_glucose between lean participants and with obesity during acute hyperglycemia.

(A) Steady state brain glucose between lean participants and with obesity during acute hyperglycemia. Bar graphs represent mean ± SD. Brain glucose was statistically significantly lower in participants with obesity, *p=0.01. (B) Correlation between BMI and steady state brain glucose during acute hyperglycemia (r=−0.57, *p=0.01). (C) T_max/CMR_glucose between lean participants and with obesity during acute hyperglycemia. Bar graphs represent mean ± SD. T_max/CMR_glucose was statistically significantly lower in participants with obesity, *p=0.04. (D) Correlation between BMI and T_max/CMR_glucose during acute hyperglycemia (r=−0.52, *p=0.03).

Figure 4.. Plasma levels of total nonesterified fatty acids (NEFA) during acute hyperglycemia compared between lean participants and with obesity and correlated with BMI.

(A) Plasma levels of NEFA in lean participants and with obesity at the end of the hyperglycemic clamp (t=120 minutes). Bar graphs represent mean ± SD. *p=0.04. (B) Correlation between NEFA and T_max/CMR_glucose during acute hyperglycemia. One data point in the obesity group is obscured by a nearly identical data point in the lean group. There was a statistically significant negative correlation between NEFA and T_max/CMR_glucose, r=−0.477, *p=0.045.