Peroxisome proliferator-activated receptor alpha and enzymes of carnitine biosynthesis in the liver are down-regulated during lactation in rats.
This study investigated the hypothesis that lactation lowers gene expression of peroxisome proliferator-activated receptor (PPAR) alpha in the liver and that this leads to a down-regulation of hepatic enzymes involved in carnitine synthesis and novel organic cation transporters (OCTNs). Thirty-two pregnant female rats were divided into 4 groups. In the first group, all pups were removed, whereas in the other groups, litters were adjusted to sizes of 4, 10, or 18 pups per dam. Dams suckling their litters, irrespective of litter size, had lower relative messenger RNA concentrations of PPARalpha, various classic PPARalpha target genes involved in fatty acid catabolism, as well as enzymes involved in carnitine synthesis (trimethyllysine dioxygenase, 4-N-trimethylaminobutyraldehyde dehydrogenase, gamma-butyrobetaine dioxygenase) and OCTN1 in the liver than dams whose litters were removed (P < .05). Moreover, dams suckling their litters had a reduced activity of gamma-butyrobetaine dioxygenase in the liver and reduced concentrations of carnitine in plasma, liver, and muscle compared with dams without litters (P < .05). In conclusion, the present study demonstrates for the first time that lactation leads to a down-regulation of PPARalpha and genes involved in hepatic carnitine synthesis and uptake of carnitine (OCTN1) in the liver, irrespective of litter size. It is moreover suggested that down-regulation of PPARalpha in the liver may be a means to conserve energy and metabolic substrates for milk production in the mammary gland.
Gutgesell
Anke
A
Institute of Agricultural and Nutritional Sciences, Martin-Luther-University of Halle-Wittenberg, D-06108 Halle, Saale, Germany.
Ringseis
Robert
R
Brandsch
Corinna
C
Stangl
Gabriele I
GI
Hirche
Frank
F
Eder
Klaus
K
D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007774:Lactation / Q000502:physiology*; D008098:Litter Size; D008099:Liver / Q000502:physiology*; D008297:Male; D008321:Mammary Glands, Animal / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000070590:Solute Carrier Proteins; D027981:Symporters; D050563:gamma-Butyrobetaine Dioxygenase / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D005230:Fatty Acids, Nonesterified; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; C000705567:Slc22a4 protein, rat; D000070590:Solute Carrier Proteins; D027981:Symporters; D006899:Mixed Function Oxygenases; C025931:trimethyl-lysine hydroxylase; D050563:gamma-Butyrobetaine Dioxygenase; C023095:4-N-trimethylaminobutyraldehyde dehydrogenase; D000445:Aldehyde Oxidoreductases; D002331:Carnitine