Fat accumulation in the rat during early pregnancy is modulated by enhanced insulin responsiveness

Abstract

Insulin sensitivity has been implicated in the variation of fat accumulation in early gestation by as-yet-unknown mechanisms. In the present study, we analyzed the insulin sensitivity of lipolysis and lipogenesis in lumbar adipocytes from rats at 0, 7, 14, and 20 days of gestation. In adipocytes of 7-day pregnant rats, we found a twofold decrease in both β-agonist (isoproterenol and BRL-37344)-stimulated lipolysis and β3-adrenoceptor protein but not in lipolysis initiated by forskolin or isobutylmethylxanthine, suggesting a modification of the lipolytic pathway at the receptor level. Whereas adipocytes from 7-day pregnant rats showed a twofold increase in fatty acid synthesis from glucose, those from 20-day pregnant animals displayed a decreased lipogenic activity. Insulin responsiveness of the lipolytic and lipogenic pathways was analyzed by dose-response experiments, giving evidence for the involvement of improved insulin responsiveness in the enhanced lipogenic and reduced lipolytic activities of adipocytes in early pregnancy. In contrast, insulin resistance is responsible for lower antilipolytic and lipogenic actions of insulin in late pregnant animals. In conclusion, the present study shows that enhanced adipose tissue insulin responsiveness during early pregnancy contributes to maternal fat accumulation, whereas decreased insulin responsiveness during late gestation modulates fat breakdown.

Fasting-induced adipose factor identified as a key adipokine that is up-regulated in white adipose tissue during pregnancy and lactation in the rat

“…Taken together, it appears that leptin, adiponectin and resistin are not playing obvious roles in the metabolic adaptations that occur in normal pregnancy and lactation. The development of insulin resistance in late pregnancy (Ramos et al 2003) does not appear to be accompanied by the expected decrease in adiponectin expression and increase in resistin expression as occurs in other insulin-resistant states (Steppan et al 2001, Weyer et al 2001. However, major changes in their expression may signal pathological states such as gestational diabetes (Kautzky-Willer et al 2001, Worda et al 2004, Thyfault et al 2005.…”

“…In the light of this, considerable effort is being put into determining whether these adipokines have a role in the regulation of homeostasis during pregnancy and lactation (Henson & Castracane 2000, Reitman et al 2001, Catalano et al 2006. Hyperleptinaemia occurs from mid to late pregnancy in rodents (Chein et al 1997, Kawai et al 1997, Tomimatsu et al 1997, Amico et al 1998, López-Soriano et al 1998, García et al 2000, Mistry & Romsos 2002, Seeber et al 2002, Ramos et al 2003, Ladyman & Grattan 2004 and humans (Butte et al 1997, Mukherjea et al 1999. However, it is debatable whether the hyperleptinaemia contributes to the metabolic adaptations; it is more likely that it is caused, at least in part, by the increase in total WAT mass rather than being an adaptive response to pregnancy.…”

Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

“…Yurena Vivas, 1 Monica Díez-Hochleitner, 1,2 Adriana Izquierdo-Lahuerta, 1 Patricia Corrales, 1 Daniel Horrillo, Pregnancy requires adaptation of maternal energy metabolism, including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth.…”

“…However, the fact that some individuals with morbid obesity maintain a healthy metabolism (5) in contrast to the inappropriate excessive IR observed in overweight individuals with central The second phase is characterized by lipolysis and insulin resistance (IR) during late stages of pregnancy, which facilitates mobilization of fuel to support the increased energy demands of late fetal growth (1).…”

The Importance of Lipid and Lipoprote in Ratios in Interpretetions of Hyperlipidaemia of Pregnancy

“…The lower lipolytic activity together with the augmented capacity of the tissues for the synthesis of glycerol-3-phosphate for uses in TG synthesis from both glucose and intracellular released glycerol results in net intracellular accumulations of TGs. Since all these pathways are stimulated by insulin, it is proposed that the enhanced insulin responsiveness [37] in the presence of an augmented response of the pancreatic β-cells to the insulinotropic stimulus of glucose that has been found in early pregnant women [38] would be the principal driving forces for the net fat depot accumulation at this stage of pregnancy. These ultimately lead to maternal fat accumulations in the anabolic phase of gestation.…”