Figure 4: Effects of peripheral (2-¹³C) acetate or intragastric (U-¹³C) inulin administrations on hypothalamic and cerebral metabolism.

(a) Representative ¹³C (125.03 MHz) HR-MAS spectra (4 °C, 5 kHz) of the hypothalamus from a mouse fasted overnight, 15 min after i.p. [2-¹³C] acetate administration (500 mg kg⁻¹). Inset: Representative ¹³C HR-MAS spectra (28–38 p.p.m.) from the hypothalamus of an overnight-fasted mouse, 180 min after [U-¹³C] inulin administration (100 mg) by gavage. (b) Increases in ¹³C incorporation into the acetate C2, GABA C2, Glu C4, Gln C4 and Lac C3 carbons (mean+s.d.) in the hypothalamus and remaining brain biopsies, following 0, 15, 30 min i.p. [2-¹³C] acetate (n=18) or 180 min intragastric [U-¹³C] inulin administrations *P<0.05, **P<0.01, ***P<0.001 (n=4). (c) Summary of the effects of [2-¹³C] acetate or [U-¹³C] inulin administrations in hypothalamic metabolism. Extracellular [2-¹³C] or ¹³C₂ acetate derived from plasma or cerebrospinal fluid are transported primarily to the astrocytes, where they are metabolized oxidatively in the TCA cycle, labelling astrocytic glutamate C4 and glutamine C4 that exchange with the corresponding neuronal pools through the glutamate–glutamine cycle, labelling GABA only in gabaergic neurons. (2-¹³C) or ¹³C₂ acetate are also oxidatively recycled in the neuronal cycle, originating the Lac C3 resonance. The glutamate–glutamine and GABA cycles support glutamatergic and gabaergic neurotransmissions, the two fundamental synaptic events triggering increased Ca²⁺ uptake and competitive Mn²⁺ uptake (MEMRI) that determine the appetite impulse.