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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Research Project #438079

Research Project: Adipocyte Gap Junction on Milk Production and Milk Quality & Hypothalamic Regulation on Lactational Hyperphagia

Location: Children's Nutrition Research Center

2020 Annual Report


Objectives
Objective 1. In wild-type animals and transgenic animals lacking a functional Connexin43 gap junction within the adipocyte, characterize the effects of Connexin43 deletion on (1) the quantity of the milk a dam produces; (2) the composition of the milk, especially the lipid composition; and (3) other non-nutritional components in the milk. Objective 2. Characterize the effects of a dam's adipocyte Connexin43 gap junction ablation on her offspring's body weight, adipose tissue mass, and late-life responses to metabolic challenges such as overnutrition.


Approach
Adipocytes, the primary cell type in the non-lactating breast, display a drastic morphological change during the lactation in rodent studies: lipid-filled cells undergo lipolysis to provide fatty acids for triglyceride synthesis and also as an energy source to support milk production; they come back as lipid-laden cells once the animal is done lactating. Our objective is to assess whether breast-milk composition can be regulated by maternal adipose tissue physiology – more specifically, adipose tissue gap junction. The results of this research can be leveraged to improve milk quantity and quality to benefit infant growth and future metabolic status. The central hypothesis is that adipose tissue responds to metabolic and hormonal cues to support milk production and that the Connexin43 gap junction is required to facilitate this process by coupling a group of adipocytes together. Genetic manipulation of adipose tissue Connexin43 will be used to determine the effects of Connexin43 deletion on milk production and milk composition as well as on the offspring's metabolic health.


Progress Report
Our research involves experimenting on an animal model with adipose tissue-specific Connexin43 gene deletion. During fiscal year 2020, the animal protocol AN-8158 has been amended and approved for breeding and using those animals. According to the research plan, we will expand the animal colony to obtain enough mice ready for the experiment. But due to the COVID-19 and colony reduction mandated by Baylor College of Medicine, we had to reduce our adipose tissue-specific Connexin43 knockout mouse colony to two cages, only sufficient for line reservation. This year our lab has recruited a research technician and trained him with techniques needed to carry out the animal breeding, genotyping, and milk collection outlines in the research proposal. We also purchased reagents required to carry out the proposed experiments in Objective 1.


Accomplishments