Pregnancy Effects on Rat Adipose Tissue Lipolytic Capacity are Dependent on Anatomical Location (original) (raw)

Circulating metabolite utilization by periuterine adipose tissue in situ in the pregnant rat

Metabolism, 1991

To study the use of glucose for lipid synthesis by the periuterine adipose tissue in situ, "C-glucose was infused through the left uterine artery of anesthetized, fed pregnant and virgin control rats. A greater amount of "C-lipid always appeared in the adipose tissue from the left uterine horn than in the tissue from the right uterine horn, indicating direct utilization of the infused "C-glucose by the tissue. Glucose utilization for both glyceride glycerol and fatty acid synthesis increased from day 0 (virgin rats) to day 20 of gestation and then decreased dramatically on day 21. In virgin and 12-day pregnant rats, glucose was incorporated into either lipidic moiety at similar rates, whereas in late pregnant rats glucose utilization for glyceride glycerol synthesis was four to five times greater than for fatty acids. The utilization of circulating fatty acids and the lipoprotein triglyceride-derived fatty acids was studied by infusing %palmitate or "C-triolein-labeled very-low-density lipoprotein (VLDL) through the left uterine artery in both virgin and 20-day pregnant rats. Incorporation of fatty acids from either one of these plasma sources was significantly higher in the pregnant than in virgin rats. This high amount of fatty acid acquisition did not account for the very active glyceride glycerol synthesis observed in pregnant rats and can only be explained by the intracellular reesterification of some lipolitic fatty acids. The results suggest a highly accelerated triacylglycerol/fatty acid substrate cycle in adipose tissue during late pregnancy, which would allow active esterification (contributing to fat accumulation) and responsive lipolysis (permitting rapid fat mobilization) by the mother.

Pregnancy modifies the ␣ 2- ␤ -adrenergic receptor functional balance in rabbit fat cells

The Journal of Lipid Research

The sympathetic nervous system controls lipolysis in fat by activation of four adrenergic receptors: ␤ 1, ␤ 2, ␤ 3, and ␣ 2. During pregnancy, maternal metabolism presents anabolic and catabolic phases, characterized by modifications of fat responsiveness to catecholamines. The contributions of the four adrenergic receptors to adipocyte responsiveness during pregnancy have never been studied. Our aim was to evaluate the influence of pregnancy on adrenergic receptor-mediated lipolysis in rabbit white adipocytes. Functional studies were performed using subtypeselective and non-selective adrenergic receptor agonists. Overall adrenergic responsiveness was measured with the physiological agonist epinephrine. Non-adrenergic agents were used to evaluate different steps of the lipolytic cascade. The ␣ 2-and ␤ 1/ ␤ 2-adrenergic receptor numbers were determined with selective radioligands. Non-adrenergic agents revealed that pregnancy induced an intracytoplasmic modification of the lipolytic cascade in inguinal but not in retroperitoneal adipocytes. Pregnancy induced an increase in ␤ 1-and specially ␤ 3-mediated lipolysis. The amounts of adipocyte ␤ 1/ ␤ 2-and ␣ 2-adrenergic receptors were increased in pregnant rabbits. Epinephrine effects revealed an increased contribution of ␣ 2-adrenergic receptor-mediated antilipolysis in adipocytes from pregnant rabbits. These results indicate that pregnancy regulates adipocyte responsiveness to catecholamines mainly via the ␣ 2-and ␤ 3-adrenergic pathways. Pregnancy induces an intracytoplasmic modification of the lipolytic cascade, probably via hormone-sensitive lipase, with differences according to fat location.-Bousquet-Mélou, A

Pregnancy modifies the α2-β-adrenergic receptor functional balance in rabbit fat cells

Journal of Lipid Research, 1999

Lipoprotein lipase and hormone-sensitive lipase activity and mRNA in rat adipose tissue during pregnancy

American Journal of Physiology-endocrinology and Metabolism, 1994

To investigate the factors controlling maternal depot fat accumulation during early pregnancy and net decrease during late pregnancy, the activity and mRNA expression of adipose tissue lipoprotein lipase (LPL) and hormonesensitive lipase (HSL) were related to several other lipid metabolic parameters. Virgin control rats, pregnant rats (at days 12, 15, 19, and 21), and lactating rats (at days 5 and 10 postpartum) were studied.

Lipid Metabolism During Pregnancy and its Implications for Fetal Growth

Current Pharmaceutical Biotechnology, 2014

More glucose crosses the placenta than any other substrate, but correlations between its concentration in maternal plasma and fetal growth are not found consistently. The accumulation of maternal fat depots and hyperlipidemia are the two principal changes in lipid metabolism during pregnancy. Although lipids cross the placenta with difficulty, maternal plasma triacylglycerols (TAG) and non-esterified fatty acids (NEFA) correlate with fetal lipids, fetal growth and fat mass under certain conditions. In intrauterine growth restriction, impaired placental transfer of lipophilic compounds (long-chain polyunsaturated fatty acids and lipophilic vitamins) seems to underpin metabolic dysfunction and decreased birth weight. In gestational diabetes mellitus (GDM), maternal TAG and NEFA levels correlate with neonatal anthropometric measures. In GDM, adipocyte fatty acid-binding protein in fetuses correlated with neonatal fat mass; changes in maternal or cord blood leptin, retinol binding protein 4 and adiponectin concentrations have been related to neonatal fat mass or birth weight, although their importance remains to be investigated. The angiopoietin-like protein 4 (ANGPTL-4) is secreted from adipose tissue, liver and placenta, and irreversibly inhibits lipoprotein lipase (LPL) activity. Maternal plasma ANGPTL-4 is decreased in GDM, and it has been proposed to be responsible for an increase in placental LPL activity, which would facilitate a greater fatty acid placental transfer, contributing to the higher fetal fat accumulation. Thus, while evidence suggesting major involvement of maternal lipid metabolism in fetal adiposity and growth exists, the precise mechanisms remain to be elucidated.

Expression in the Perirenal Adipose Tissue of Late Gestation Fetal Sheep

Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We have investigated whether PR alters expression of genes which regulate adipogenesis (IGF1, IGF1R, IGF2, IGF2R, PPAR , RXR ), adipocyte metabolism (LPL, G3PDH, GAPDH) and adipokine signalling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in non pregnant ewes prior to mating. Fetal blood samples were collected from 116d gestation and perirenal visceral adipose tissue (PAT) collected from PR and control fetuses at 145d. PAT gene expression was measured by qRT-PCR. PR fetuses had a lower weight (PR 2.90 ± 0.32 kg; Control, 5.12 ± 0.24 kg; P<0.0001), mean gestational arterial PO 2 (P<0.0001), plasma glucose (P<0.01) and insulin concentrations (P<0.02), than Controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR 0.332 ± 0.063; Control 0.741 ± 0.083; P<0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR 0.077 ± 0.009; Control, 0.115 ± 0.013; P<0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus restriction of placental and hence fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue which may alter the functional development of the perirenal fat depot and contribute to altered leptin signalling in the growth restricted new born and the subsequent emergence of an increased visceral adiposity. Rosberg S. Longitudinal follow-up of growth in children born small for gestational age. Acta Paediatr 82: 438-443, 1993. 3. Alkalay AL GJ, Pomerance JJ. Evaluation of neonates born with intrauterine growth retardation: review and practice guidelines. J Perinatol 18: 142-151, 1998. 4. Ambrosini G, Nath AK, Sierra-Honigmann MR, and Flores-Riveros J. Transcriptional activation of the human leptin gene in response to hypoxia. Involvement of hypoxia-inducible factor 1. Inhibition of p38MAPK Increases Adipogenesis From Embryonic to Adult Stages. Diabetes 55: 281-289, 2006. 6. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, and Clark PM. Type 2 (noninsulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36: 62-67, 1993. 7. Bavdekar A, Yajnik CS, Fall CH, Bapat S, Pandit AN, Deshpande V, Bhave S, Kellingray SD, and Joglekar C. Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? Diabetes 48: 2422-2429, 1999. 8. Circulating insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs) and tissue mRNA levels of IGFBP-2 and IGFBP-4 in the ovine fetus. J Endocrinol 145: 545-557, 1995. 11. Considine RV, Nyce MR, Morales LM, Magosin SA, Sinha MK, Bauer TL, Rosato EL, Colberg J, and Caro JF. Paracrine stimulation of preadipocyte-enriched cell cultures by mature adipocytes. Am J Physiol Endocrinol Metab 270: E895-899, 1996. 12. Curhan GC, Willett WC, Rimm EB, Spiegelman D, Ascherio AL, and Stampfer MJ. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 94: 3246-3250, 1996. 13. Lamb. Endocrinology 148: 1350-1358, 2007. 14. De Blasio MJ, Gatford KL, Robinson JS, and Owens JA. Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb. Am J Physiol Regul Integr Comp Physiol 292: R875-886, 2007. 15. Economides D, Nicolaides K, and Campbell S. Metabolic and endocrine findings in appropriate and small for gestational age fetuses. J Perinat Med 19: 97-105, 1991. 16. Edwards LJ, Symonds ME, Warnes KE, Owens JA, Butler TG, Jurisevic A, and McMillen IC. Responses of the fetal pituitary-adrenal axis to acute and chronic hypoglycemia during late gestation in the sheep. Endocrinology 142: 1778-1785, 2001. 17. Ehrhardt RA, Bell AW, and Boisclair YR. Spatial and developmental regulation of leptin in fetal sheep. DJ. Size at birth, childhood growth and obesity in adult life. Int J Obes Relat Metab Disord 25: 735-740, 2001. 20. Faust IM, Johnson PR, Stern JS, and Hirsch J. Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol Endocrinol Metab 235: E279-286, 1978. 21. Fitzhardinge PM and Steven EM. The small-for-date infant. I. Later growth patterns. Pediatrics 49: 671-681, 1972. 22. Gong DW, Bi S, Pratley RE, and Weintraub BD. Genomic structure and promoter analysis of the human obese gene. J Biol Chem 271: 3971-3974, 1996. 23. Greenwood PL, Hunt AS, Hermanson JW, and Bell AW. Effects of birth weight and postnatal nutrition on neonatal sheep: I. Body growth and composition, and some aspects of energetic efficiency. J Anim Sci 76: 2354-2367, 1998. 24. Gregoire FM, Smas CM, and Sul HS. Understanding adipocyte differentiation. Physiol Rev 78: 783-809, 1998. 25. Grosfeld A, Andre J, Hauguel-De Mouzon S, Berra E, Pouyssegur J, and Guerre-Millo M. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J Biol Chem 277: 42953-42957, 2002. 26. He Y, Chen H, Quon MJ, and Reitman M. The mouse obese gene. Genomic organization, promoter activity, and activation by CCAAT/enhancer-binding protein alpha. M, Yoshimasa Y, Nishi S, and et al. Structural organization and chromosomal assignment of the human obese gene. 33. Jaquet D, Gaboriau A, Czernichow P, and Levy-Marchal C. Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J Clin Endocrinol Metab 85: 1401-1406, 2000. 34. Jaquet D, Gaboriau A, Czernichow P, and Levy-Marchal C. Relatively low serum leptin levels in adults born with intra-uterine growth retardation. International Journal of Obesity & Related Metabolic Disorders 25: 491, 2001. 35. Jaquet D, Leger J, Levy-Marchal C, Oury JF, and Czernichow P. Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation on serum leptin concentrations. 20 36. Jaquet D, Leger J, Tabone MD, Czernichow P, and Levy-Marchal C. High serum leptin concentrations during catch-up growth of children born with intrauterine growth retardation. J Clin Endocrinol Metab 84: 1949-1953, 1999. 37. Kauter K, Ball M, Kearney P, Tellam R, and McFarlane JR. Adrenaline, insulin and glucagon do not have acute effects on plasma leptin levels in the sheep: development and characterisation of an ovine leptin ELISA. J Endocrinol 166: 127-135, 2000. 38. Kind KL, Owens JA, Robinson JS, Quinn KJ, Grant PA, Walton PE, Gilmour RS, and Owens PC. Effect of restriction of placental growth on expression of IGFs in fetal sheep: relationship to fetal growth, circulating IGFs and binding proteins. J Endocrinol 146: 23-34, 1995. 39. Lau D, Shillabeer G, Wong K, Tough S, and Russell J. Influence of paracrine factors on preadipocyte replication and differentiation. Int J Obes Relat Metab Disord 14: 193-201, 1990. 40. Law CM, Barker DJ, Osmond C, Fall CH, and Simmonds SJ. Early growth and abdominal fatness in adult life. J Epidemiol Community Health 46: 184-186, 1992. 41. Leger J, Levy-Marchal C, Bloch J, Pinet A, Chevenne D, Porquet D, Collin D, and Czernichow P. Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study. BMJ 315: 341-347, 1997. 42. LeRoith D, Werner H, Beitner-Johnson D, and Roberts CT, Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16: 143-163, 1995. 43. Levy-Marchal C, Jaquet D, and Czernichow P. Long-term metabolic consequences of being born small for gestational age. Semin Neonatol 9: 67-74, 2004. 44. Lithell HO, McKeigue PM, Berglund L, Mohsen R, Lithell UB, and Leon DA.

Sex steroid receptor expression in different adipose depots is modified during midpregnancy

Molecular and Cellular Endocrinology, 2006

Sex hormone signalling is key in the understanding of adipose tissue metabolism during pregnancy. Sex hormones play an important role in adipose tissue metabolism by activating specific receptors that alter several steps of lipolysis and lipogenesis. We analyze steroid receptor mRNA levels in different rat adipose depots and mammary fat pad, as well as the sex hormone profile during midpregnancy, coinciding with the placentation process. Thus, progesterone and estradiol plasma levels were increased as well as testosterone levels. This hormonal profile was accompanied by low glucose to insulin ratio. PR-B, ER␣ and AR receptor densities during midpregnancy were dependent on adipose depot location. In mammary fat pad, the mRNA levels of sex hormone receptors were correlated with the growth of the depot. These results demonstrate that sex steroid hormone receptor mRNA expression during midpregnancy is tissue-specific. Our results agree with the idea that the increased estrogenic and androgenic signalling could be addressed to reducing the lipogenic state in early pregnancy exerted mainly by progesterone and to prepare adipose tissue for the beginning of the catabolic phase in late pregnancy in a depot-specific manner.

Changes in mammary fat pad composition and lipolytic capacity throughout pregnancy

Cell and Tissue Research, 2006

Changes in rat mammary fat pad during pregnancy were assessed by studying differences in the morphology and composition of the pad and in the levels of proteins involved in the accumulation and mobilization of fat stores. During pregnancy, the mammary fat pad weight had increased 1.8-fold by day 20, as compared with control rats. DNA content had increased two-fold by day 13 and remained stable until day 20. Protein content showed a two-fold increase on day 20, compared with control rats. As pregnancy advanced, both the percentage of mammary gland cells with respect to the whole mammary fat pad and the size of the adipocytes increased. The specific content of the different elements of the lipolytic pathway, viz. α 2Aadrenergic receptor (AR), β 3 -AR, cAMP-dependent protein kinase and hormone-sensitive lipase (HSL), underwent a decrease as pregnancy progressed, although adenylate cyclase increased greatly. The lipoprotein lipase (LPL) content per gram of tissue increased with pregnancy and the HSL-to-LPL ratio reflected a continuous increase in triglyceride storage throughout pregnancy. Thus, the mam-mary fat pad undergoes extensive morphological, compositional and metabolic transformation during pregnancy, attributable to the development of the mammary gland. The various elements of the lipolytic pathway and LPL undergo major changes during the development of the mammary gland focused towards the increase of fat stores and allowing the accumulation of lipid droplets in the epithelial mammary cells and an increase in adipocyte size.

Endocrine and nutritional regulation of fetal adipose tissue development

Journal of Endocrinology, 2003

In the fetus, adipose tissue comprises both brown and white adipocytes for which brown fat is characterised as possessing the unique uncoupling protein (UCP)1. The dual characteristics of fetal fat reflect its critical role at birth in providing lipid that is mobilised rapidly following activation of UCP1 upon cold exposure to the extra- uterine environment. A key stage in the

Adaptations in lipid metabolism of bovine adipose tissue in lactogenesis and lactation

Journal of Lipid Research, 1986

The timing and magnitude of metabolic adaptations in adipose tissue during lactogenesis and lactation were determined in first lactation bovines. In vitro rates of lipogenesis and palmitate esterification were measured to estimate in vivo synthesis. Lipolysis was measured in the basal state and as maximally stimulated by norepinephrine or epinephrine to estimate physiological adaptations as well as the changes in catecholamine responsiveness. Subcutaneous adipose tissue was biopsied ati,-0.5, +0.5, 1, 2, and 6 months from parturition. From 1 to 0.5 months prepartum there was a 54% reduction in lipogenesis, a 16% reduction in esterification, a 54 and 77% increase in norepinephrine-and epinephrine-stimulated free fatty acid (FFA) release, respectively, and a 28% increase in epinephrine-stimulated glycerol release. The immediate postpartum period (0.5 and 1 month) was marked by a decrease in lipogenesis to 5% and esterification to 50% of-1 month rates. During this period, norepinephrine-stimulated FFA release increased 50% above-1 month rates, epinephrine-stimulated FFA release increased 128%, and norepinephrine-and epinephrine-stimulated glycerol release increased 30 and 8776, respectively. Midlactation (2 and 6 months) was marked by a dramatic rebound in lipogenesis and esterification to 14-fold and 2.5-fold prepartum rates, respectively. Basal glycerol release doubled during this period, while basal FFA release declined to near prepartum levels. Catecholaminestimulated FFA and glycerol release decreased from the peak during midlactation, but remained elevated compared to prepartum 1evels.lBovine adipose tissue adapts prepartum for increased release of energy, meets peak lactation demand by ceasing synthesis and increasing lipolysis, and recovers synthesis dramatically to replenish body energy stores while also maintaining elevated levels of lipolysis in support of lactation.