Reduction of mammary and liver lipogenesis and alteration of milk composition during lactation in rats by hypothyroidism.
OBJECTIVE
The profound impairment in litter growth produced by untreated maternal hypothyroidism (HypoT) may be a consequence of maternal metabolic dysfunctions affecting lactation. In this work we studied the effects of HypoT on mammary and liver lipid metabolism and its consequences on milk quality.


METHODS
We studied the effects of prolonged 6-propyl-2-thiouracil (PTU)-induced HypoT (0.01% PTU in drinking water starting 8 days before mating until sacrifice) on milk macronutrient composition, liver and mammary lipid metabolism and content and serum lipid, and glucose and insulin concentrations in rats on days 7, 15 (L15), and 20 (L20) of lactation. Mammary and hepatic mRNA abundances of lipogenic enzymes were measured using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on L15 and L20.


RESULTS
Milk lactose and triglycerides (TG) were reduced by HypoT, as well as mammary acetyl CoA carboxylase (ACC) activity on L15 and L20, and ACC and lipoprotein lipase (LPL) mRNA on L20. HypoT also decreased hepatic ACC activity on both days, ACC mRNA on L15 and liver [(3)H]H(2)O incorporation to TGs and TG content on L20. HypoT diminished insulinemia, increased serum total lipids, and decreased serum TGs on some or all the days of lactation studied.


CONCLUSIONS
HypoT produces a drastic decrease in milk TGs; the main cause for this seems to be the decreases in liver TG synthesis and in circulating TGs, which, along with reduced mammary uptake of fatty acids caused by decreased LPL expression and possibly diminished mammary lipogenesis, result in an impaired mammary output of TGs to the milk. Thus, the impaired growth of the litters of HypoT mothers can be largely attributed to the low milk quality along with the impaired milk ejection.
Hapon
María Belén
MB
Laboratorio de Reproducción y Lactancia, IMBECU, CRICYT-CONICET, Mendoza, Argentina.
Varas
Silvia M
SM
Giménez
María S
MS
Jahn
Graciela A
GA
D000818:Animals; D000833:Animals, Suckling; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D007037:Hypothyroidism / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007774:Lactation / Q000502:physiology; D007775:Lactation Disorders / Q000209:etiology / Q000378:metabolism*; D007785:Lactose / Q000378:metabolism; D050155:Lipogenesis / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008892:Milk / Q000378:metabolism; D008893:Milk Ejection / Q000502:physiology; D008894:Milk Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014280:Triglycerides / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D008894:Milk Proteins; D014280:Triglycerides; D014284:Triiodothyronine; D013972:Thyrotropin; D007785:Lactose; D013974:Thyroxine