Increased Brain Fatty Acid Uptake in Metabolic Syndrome

Abstract

OBJECTIVETo test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.RESEARCH DESIGN AND METHODSWe measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention.RESULTSAt baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%.CONCLUSIONSTo our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction.

Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes

“…Although the reason for this difference is unknown, this could be related to a lower number of astrocytes in cortical versus hypothalamic areas (52) and/or differences in the expression of proteins and enzymes involved in LCFA metabolism (LCFA transporters, acyl-CoA synthase, and CPT-1) that may affect LCFA uptake. Nonetheless, our results are consistent with previous reports showing regional differences in palmitate oxidation and incorporation in rat (51,53) or human brain (54) and high levels of palmitate incorporation in the arcuate nucleus compared with non-hypothalamic areas (53) after systemic administration of radiolabeled palmitate tracers. In addition, in agreement with the former study in vivo (53), we found here that palmitate oxidation rate in MBH and cortical slices was proportional to the rate of glucose utilization.…”

Hypothalamic dysfunction in obesity

“…Recently, however, the uptake of fatty acids by the brain has been demonstrated using stable isotopes and positron emission tomography and was found to be increased in individuals with the metabolic syndrome and to subsequently decline after weight loss (114) . Apart from the use of lipids as an energy source in the brain it has become increasingly apparent that lipids and lipid metabolism play an important role in the regulation of energy balance by the hypothalamus.…”

P3–076: Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes

“…In particular, the concentration of palmitate almost doubled as compared to control, above 1100 g/L in the CSF of traumatic brain injury versus around 600 g/L in control (Pilitsis et al, 2003;Pilitsis et al, 2001;Zamir et al, 1991). FFAs in plasma can cross the blood-brain barrier (Dhopeshwarkar and Mead, 1973;Smith and Nagura, 2001), and high fat diets increase the uptake of fatty acids by the brain from the plasma (Karmi et al, 2010;Wang et al, 1994). The concentration of FFAs in normal human plasma in vivo generally ranges between 0.3-1.0mM (Dole, 1956;Shultz, 1991;Tikanoja et al, 1989).…”