Moderate calorie restriction during gestation programs offspring for lower BAT thermogenic capacity driven by thyroid and sympathetic signaling.
BACKGROUND
Maternal calorie restriction during pregnancy programs offspring for later overweight and metabolic disturbances. Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and has recently emerged as a very likely target for human obesity therapy.


OBJECTIVE
Here we aimed to assess whether the detrimental effects of undernutrition during gestation could be related to impaired thermogenic capacity in BAT and to investigate the potential mechanisms involved.


METHODS
Offspring of control and 20% calorie-restricted rats (days 1-12 of pregnancy) (CR) were studied at the age of 25 days. Protein levels of uncoupling protein 1 (UCP1) and tyrosine hydroxylase (TyrOH); mRNA levels of lipoprotein lipase (LPL), carnitine palmitoyltransferase 1 (CPT1) and deiodinase iodothyronine type II (DIO2) in BAT; and blood parameters including thyroid hormones, were determined. The response to 24-h cold exposure was also studied by measuring body temperature changes over time, and final BAT UCP1 levels.


RESULTS
Compared with controls, CR animals displayed in BAT lower UCP1 and TyrOH protein levels and lower LPL and CPT1 mRNA levels; they also showed lower triiodothyronine (T3) plasma levels. CR males, but not females, revealed lower DIO2 mRNA levels than controls. When exposed to cold, CR rats experienced a transient decline in body temperature, but the values were reestablished after 24 h, despite having lower UCP1 levels than controls.


CONCLUSIONS
These results suggest that BAT thermogenic capacity is diminished in CR animals, involving impaired BAT sympathetic innervation and thyroid hormone signaling. These alterations make animals more sensitive to cold and may contribute to long-term outcomes of gestational calorie restriction in promoting obesity and related metabolic alterations.
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
M
M
Palou
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
T
T
Priego
Department of Nutrition and Food Sciences, Faculty of Biology, University of Barcelona and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain.
M
M
Romero
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
N
N
Szostaczuk
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
J
J
Konieczna
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
C
C
Cabrer
Department of Nutrition and Food Sciences, Faculty of Biology, University of Barcelona and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain.
X
X
Remesar
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
A
A
Palou
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
C
C
Pico
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction / Q000009:adverse effects*; D005260:Female; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000378:metabolism*; D022722:Thermogenesis; D013961:Thyroid Gland / Q000378:metabolism*