Deficits in brain glucose transport among younger adults with obesity

• Published in: Obesity (Silver Spring, Md.) Md.), 2024-07, Vol.32 (7), p.1329-1338
• Main Authors: Gunawan, Felona, Matson, Brooke C., Coppoli, Anastasia, Jiang, Lihong, Ding, Yuyan, Perry, Rachel, Sanchez‐Rangel, Elizabeth, DeAguiar, Renata Belfort, Behar, Kevin L., Rothman, Douglas L., Mason, Graeme F., Hwang, Janice J.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Cardiovascular disease; Catheters; Diabetes; Fatty acids; Glucose; Hyperglycemia; Insulin resistance; Magnetic resonance imaging; Metabolism; Obesity; Plasma; Spectrum analysis
• ISSN: 1930-7381; 1930-739X; 1930-739X
• DOI: 10.1002/oby.24034

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 (Tmax/CMRglucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (VTCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and Tmax/CMRglucose (r = −0.477; p = 0.045). Conclusions We conclude that CMRglucose is unlikely to differ between groups due to similar VTCA, and, therefore, the glucose transport Tmax 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.