TY - JOUR

T1 - Food intake regulation during pregnancy and lactation in mice with reduced activity of the melanocortin system

AU - Makarova, E. N.

AU - Romanova, I. V.

AU - Bazhan, N. M.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Activation of melanocortin receptors (MCRs) in the hypothalamus inhibits appetite. Neuropeptide Y (NPY) and Agouti Related Protein (AgRP) are coexpressed in some hypothalamic neurons, and stimulate feeding: NPY, via the inhibition of MCR-expressing neurons; and AgRP, via the MCR4 antagonism. The yellow mutation at the mouse agouti locus (Ay) evokes MCR blockage and stimulates appetite in nonbreeding females. However, the role of MCRs in food intake regulation during pregnancy and lactation is unclear. In this study, we measured the Agrp and Npy mRNA levels in hypohalamus in virgin and breeding C57Bl a/a (control) and Ay/a females during pregnancy (on days 7, 13, 18), lactation (days 10 and 21), and after the separation of offspring, as well as AgRP immunoreactivity in virgin and lactating females, and correlated gene and protein expression with food intake. Virgin Ay/a females presented higher food intake compared to a/a controls, and showed lower Agrp mRNA and protein levels. Pregnant Ay/a and a/a mice differed in patterns of food intake and neuropeptide expression. Npy mRNA levels increased during pregnancy only in a/a mice, while Agrp mRNA levels increased in both genotypes, being lower in Ay/a mice. In lactating Ay/a and a/a mice, the Agrp and Npy mRNA levels were similar. The AgRP protein content was higher in lactating than in virgin Ay/a mice. The obtained results demonstrate that, the MCR blockage inhibits Agrp expression in nonbreeding female mice, but not in lactating mice. Thus, during pregnancy, food intake regulation involves MCR signaling and activation of the Npy and Agrp expression. However, in lactating dams, hyperphagia is independent of the MCR blockade.

AB - Activation of melanocortin receptors (MCRs) in the hypothalamus inhibits appetite. Neuropeptide Y (NPY) and Agouti Related Protein (AgRP) are coexpressed in some hypothalamic neurons, and stimulate feeding: NPY, via the inhibition of MCR-expressing neurons; and AgRP, via the MCR4 antagonism. The yellow mutation at the mouse agouti locus (Ay) evokes MCR blockage and stimulates appetite in nonbreeding females. However, the role of MCRs in food intake regulation during pregnancy and lactation is unclear. In this study, we measured the Agrp and Npy mRNA levels in hypohalamus in virgin and breeding C57Bl a/a (control) and Ay/a females during pregnancy (on days 7, 13, 18), lactation (days 10 and 21), and after the separation of offspring, as well as AgRP immunoreactivity in virgin and lactating females, and correlated gene and protein expression with food intake. Virgin Ay/a females presented higher food intake compared to a/a controls, and showed lower Agrp mRNA and protein levels. Pregnant Ay/a and a/a mice differed in patterns of food intake and neuropeptide expression. Npy mRNA levels increased during pregnancy only in a/a mice, while Agrp mRNA levels increased in both genotypes, being lower in Ay/a mice. In lactating Ay/a and a/a mice, the Agrp and Npy mRNA levels were similar. The AgRP protein content was higher in lactating than in virgin Ay/a mice. The obtained results demonstrate that, the MCR blockage inhibits Agrp expression in nonbreeding female mice, but not in lactating mice. Thus, during pregnancy, food intake regulation involves MCR signaling and activation of the Npy and Agrp expression. However, in lactating dams, hyperphagia is independent of the MCR blockade.

KW - A mice

KW - AgRP

KW - food intake

KW - lactation

KW - melanocortin receptors

KW - NPY

KW - pregnancy

UR - http://www.scopus.com/inward/record.url?scp=85014789935&partnerID=8YFLogxK

U2 - 10.1134/S2079059717010099

DO - 10.1134/S2079059717010099

M3 - Article

AN - SCOPUS:85014789935

VL - 7

SP - 63

EP - 70

JO - Russian Journal of Genetics: Applied Research

JF - Russian Journal of Genetics: Applied Research

SN - 2079-0597

IS - 1

ER -