Enhanced lipid utilization is coupled to the sickness responses triggered by lipopolysaccharide

Whole Transcriptome Analysis of Hypothalamus in Mice during Short-Term Starvation

“…Among the 45 upregulated genes, we identified the ones that encode metabolic enzymes, such as Hmgcs2, which is involved in the synthesis of ketone bodies. In accordance with these findings, our previous studies indicated that the hunger-promoting condition triggered by fasting led to an increase in ketone bodies and a decrease in lactate in the hypothalamus, while mice retaining anorexigenic responses to lipopolysaccharide treatment revealed a contradicting pattern in the circulating levels of ketone bodies and lactate [ 32 , 33 ]. Circulating factors derived from peripheral organs, such as fat, muscle, and liver, dynamically act as signal messengers that propagate information on the current status of energy availability to integrating centers, such as the hypothalamus.…”

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

“…In this study, hypothalamic metabolites were profiled in response to short-term food deprivation and related molecular data were obtained. Previous studies indicated that the types and patterns of fuel utilization in hypothalamic cells, including appetite-regulating neurons, astrocytes, and microglia, are directly connected to the regulation of energy metabolism [ 5 , 12 , 13 ]. For instance, altered mitochondrial dynamics occurred in hypothalamic neurons of rodent models of obesity, in which cellular metabolism was genetically modified [ 4 ].…”

“…We recently reported that enhanced lipid utilization occurred in the hypothalamus of mice, retaining the negative energy balance. Intriguingly, an increase in multiple fatty acids and a specific ketone body was observed in the hypothalami of the mice, revealing sickness responses, including severe anorexia [ 12 ]. Taken together, we suggest that enhanced ketogenesis and lipid utilization during the development of negative and positive energy balances could be physiological signals to operate the hypothalamic neuronal circuit, as well as the biochemical processes that utilize alternative fuel sources.…”

“…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).…”

“…The freeze-dried sample was derivatized in 80 μL of methoxyamine hydrochloride (20 mg/mL) at 37 °C for 90 min, and then mixed with 80 μL of N,O-Bis(trimethylsilyl) trifluoroacetamide at 60 °C for 60 min. The qualitative and quantitative analyses of GC-MS data were performed using a previously described method [ 12 ].…”