The Mesencephalic Trigeminal Nucleus Controls Food Intake and Body Weight via Hindbrain POMC Projections.

Preclinical animal study investigating the role of the mesencephalic trigeminal nucleus (Mes5) in food intake and body weight regulation using pharmacological and chemogenetic manipulations in mice.

“Here, we investigate for the first time a role for Mes5 melanocortin-4 receptors (MC4Rs) in food intake and body weight regulation.”

Adult male and female mice, specifically POMC-Cre+ and MC4Rflox/flox strains.

“Adult (8 weeks old) male and female mice were used as subjects of this study.”

Varied by experimental group, including n=23 for pharmacological agonism, n=20 for antagonism, n=18 for central chemogenetic manipulation, and n=33 for peripheral chemogenetic manipulation.

“For pharmacological agonism (n = 23; n = 14 males, n = 9 females) or antagonism (n = 20; n = 12 males, n = 8 females) of the Mes5 MC4R, mice were prepared with a bilateral guide cannula”

Acute measurements of food intake and body weight at 1, 3, 6, and 24 hours post-manipulation, with chronic monitoring for 16 days in knockout experiments.

“Food intake measurements were performed by calculating the cumulative change in the weight of the food (+/−0.001 g) from the time of injection to the indicated time point (1, 3, 6, 24 h).”

The mesencephalic trigeminal nucleus (Mes5) expresses melanocortin-4 receptors (MC4R) on parvalbumin-expressing neurons.

“Expression of mRNA transcripts for the MC4R (yellow) was observed on Mes5 neurons that express parvalbumin (magenta) but not dopamine-beta-hydroxylase-expressing neurons (green) of the adjacent locus coeruleus (Figure 1).”

Pharmacological activation of Mes5 MC4Rs suppresses food intake and body weight, whereas these receptors are not necessary for food intake control.

“In both males and females, we observed food intake suppression by MTII at 3, 6, and 24 h (Figure 2A,B) as well as a suppression of body weight at 24 h (Figure 2C,D).”

Chemogenetic activation of NTS POMC projections to the Mes5 suppresses food intake.

“In NTShm3Dq mice, cumulative chow intake was suppressed for CNO relative to vehicle injected POMC-Cre+ mice at 1, 3, 6 h (Figure 5A).”

The study did not measure energy expenditure, respiratory quotient, or oxidative metabolism, and the endogenous role of the circuit requires further study.

“Lastly, our studies were limited to food intake and, as such, the potential impact of Mes5 MC4R stimulation on energy expenditure, respiratory quotient, or oxidative metabolism remains unknown.”