Premium
Sex‐selective Effects of MCH Antagonism on Metabolic Hormones
Author(s) -
Gilman Lee,
Beaver Jasmin N.,
Vasquez Erin,
Bowman Melodi A.,
Vitela Melissa,
Daws Lynette C.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04116
Subject(s) - endocrinology , medicine , leptin , hormone , endogeny , melanin concentrating hormone , insulin , blood sampling , receptor , obesity , neuropeptide
Melanin‐concentrating hormone (MCH) is a neuroactive peptide that influences eating and emotional behaviors, as well as insulin sensitivity and adiposity. The vast majority of MCH research has focused only on males. Further, how endogenous levels of MCH parallel metabolic and behavioral measures over time, or are affected by diet, has not previously been investigated. We evaluated how endogenous MCH changes, as a function of sex, in adult rats as they consumed either a control diet alone, or a control diet supplemented with a high fat/high sugar (i.e., “Western”) diet. During the final week of this 8 week dietary manipulation period, rats received daily injections of the MCH receptor 1 antagonist GW803430 (3 mg/kg) or vehicle (1 mL/kg). Weekly blood sampling for the duration of the diet manipulation allowed for measurement of circulating MCH, insulin, leptin, and glucose levels. Surprisingly, we noted that GW803430 significantly reduced endogenous MCH levels only in males consuming control diet. Endogenous insulin levels were also dramatically lowered in males receiving GW803430, independent of diet condition. Though female rats did not exhibit these hormonal changes in response to drug, they did exhibit diet‐ and drug‐specific emotional behavior responses in the forced swim test that mapped on to endogenous MCH levels. Ongoing analyses are examining leptin levels, food consumption, and hepatic steatosis in relation to endogenous MCH. To our knowledge, these are the first investigations into how MCH receptor 1 antagonism affects circulating metabolic hormones, and into how this drug affects emotional behavior in females. To confirm involvement of the MCH receptor 1 in these sex‐selective hormonal reductions and behavioral effects, future experiments will employ a different MCH receptor 1 antagonist. Support or Funding Information This work was supported by a Morrison Trust grant to LCD, a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation and Vital Projects Fund, Inc. to TLG, and National Institutes of Health grants 1R01 MH106978 and R21 DA046044 to LCD.