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

• Published in: American journal of physiology: endocrinology and metabolism 2005-06, Vol.288 (6), p.E1179-E1187
• Main Authors: Flint, David J, Travers, Maureen T, Barber, Michael C, Binart, Nadine, Kelly, Paul A
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - biosynthesis; Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Body Weight - physiology; Caseins - biosynthesis; Caseins - genetics; Caseins - metabolism; Disease Models, Animal; Eating - physiology; Female; Histocytochemistry; Lactalbumin - genetics; Lactalbumin - metabolism; Lactation - physiology; Mammary Glands, Animal - growth & development; Mammary Glands, Animal - metabolism; Mammary Glands, Animal - pathology; Mice; Milk Proteins - biosynthesis; Milk Proteins - genetics; Milk Proteins - metabolism; Obesity - metabolism; Obesity - pathology; Obesity - physiopathology; Organ Size - physiology; Pregnancy; RNA, Messenger - biosynthesis; RNA, Messenger - genetics
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00433.2004

1 Hannah Research Institute, Ayr, United Kingdom; and 2 Faculty of Medicine Rene Descartes, Institut National de la Santé et de la Recherche Médicale Unit 584, Hormone Targets, Paris, France Submitted 10 September 2004 ; accepted in final form 22 January 2005 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. high fat; acetyl-coenzyme A carboxylase; morphogenesis Address for reprint requests and other correspondence: D. J. Flint, Hannah Research Institute, Ayr KA6 5HL, UK (E-mail: d.flint{at}hannah.ac.uk )