Diet-induced obesity impairs mammary development and lactogenesis in murine mammary gland

D.J. Flint, M. Travers, M.C. Barber, N. Binart, P.A. Kelly

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Abstract

We have developed a mouse model of diet-induced obesity that shows numerous
abnormalities relating to mammary gland function. Animals ate 40% more calories when offered a high-fat diet and gained weight at three times the rate of controls. They exhibited reduced conception rates, increased peripartum pup mortality, and impaired lactogenesis. The impairment of lactogenesis involved lipid accumulation in the secretory epithelial cells indicative of an absence of copius milk secretion. Expression of mRNAs for -casein, whey acid protein, and
-lactalbumin were all decreased immediately postpartum but recovered
as lactation was established over 2–3 days. Expression of acetyl-CoA carboxylase (ACC)- mRNA was also decreased at parturition as was the total enzyme activity, although there was a compensatory increase in the proportion in the active state. By day 10 of lactation, the proportion of ACC in the active state was also decreased in obese animals, indicative of suppression of de novo fatty acid synthesis resulting from the supply of preformed fatty acids in the
diet. Although obese animals consumed more calories in the nonpregnant
and early pregnant states, they showed a marked depression in fat intake around day 9 of pregnancy before food intake recovered in later pregnancy. Food intake increased dramatically in both lean and obese animals during lactation although total calories consumed were identical in both groups. Thus, despite access to high-energy diets, the obese animals mobilized even more adipose tissue during lactation than their lean counterparts. Obese animals also exhibited marked
abnormalities in alveolar development of the mammary gland, which may partially explain the delay in differentiation evident during lactogenesis.
Original languageEnglish
Pages (from-to)E1179-87
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume288
Issue number6
DOIs
Publication statusPublished - 2005

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