Characterization of Fatty Acid Composition Underlying Hypothalamic Inflammation in Aged Mice

Abstract

Degenerative diseases, which can develop during aging, are underlined by inflammatory processes. Hypothalamic inflammation triggered by elevation in circulating fatty acid levels is directly coupled to metabolic disorders. The present study aimed to investigate and characterize the hypothalamic inflammation and composition of fatty acids in the hypothalami of aged mice. We verified that inflammation and microglial activation occur in the hypothalami of aged mice by performing quantitative real-time PCR and using immunohistochemistry methods. In addition, we observed increased levels of various saturated fatty acids in the hypothalami of aged mice, whereas no major changes in the levels of circulating fatty acids were detected using gas chromatography with a flame ionization detector. Collectively, our current findings suggest that increases in saturated fatty acid levels are coupled to hypothalamic inflammation and thereby cause perturbations in energy metabolism during the aging process.

Regulation of PPARα by APP in Alzheimer disease affects the pharmacological modulation of synaptic activity

“…By Western blot analysis with an antibody that recognizes human and mouse APP, 2- to 3-fold higher APP levels were observed in hAPP WT as compared with WT mice at early (3–4 months old: 2.67 ± 0.34), advanced (6–8 months old: 1.86 ± 0.21), and late ages (11–12 months old: 2.63 ± 0.30) ( Figure 2, A and B ) as expected ( 32 ). A trend of a higher expression of brain Ppara was observed together with a trend of increased Acox1 , Cpt1a , and Pdk4 mRNA levels along with age in WT mice ( Figure 2, C–F ), indicating that the aged brain retains enhanced FA utilization compared with young WT mice, meaning that aging brain could switch to FA oxidation ( 33 , 34 ). While a similar profile was observed in hAPP WT mice at early and advanced ages, a 2- to 5-fold decrease in Ppara , Acox1 , Cpt1a , and Pdk4 mRNA levels was observed (0.46 ± 0.04, 0.58 ± 0.06, 0.50 ± 0.10, 0.91 ± 0.06, respectively) in 11- to 12-month-old hAPP WT mice compared with WT littermates at the same age ( Figure 2, C–F ), an age at which severe cognitive deficits are detected ( 32 , 35 ).…”

Long-term diet-induced obesity does not lead to learning and memory impairment in adult mice

“…Further, it was recently demonstrated that microglia, bone-marrow derived macrophages, may maintain their pool without significant substitution by circulating monocytes after their establishment in early postnatal life, even under conditions of chronic HFD feeding [ 70 ]. Here, for immunofluorescence labeling of microglial cells in hypothalamic sections, we used Iba1, which is a molecular marker for active microglia participating in membrane ruffling and phagocytosis [ 59 ]. Iba1 is also known to increase the expression of inflammatory chemokines and cytokines [ 71 ].…”

“…The total staining intensity was expressed by integrated density (mean gray value x area) using the ROI manager and the background subtraction function of ImageJ. The reactive state of microglial cells is frequently measured by fluorescence intensity of Iba1 or by percentage of Iba1-stained area [ 37 , 45 , 56 – 59 ].…”

Metabolic Profiling of the Hypothalamus of Mice during Short-Term Food Deprivation

“…The extraction and analysis procedures from the serum and hypothalamus were described in a previous report [ 12 , 26 ]. Briefly, the serum (0.1 mL) was extracted with 0.3 mL of 3:1 ( v / v ) methanol:chloroform and 0.03 mL of internal standard (IS, 2-chloro-L-phenylalanine, 300 μg/mL).…”