Implication of Low Level Inflammation in the Insulin Resistance of Adipose Tissue at Late Pregnancy

Abstract

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

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

“…fat distribution (6)(7)(8) suggests that the absolute amount of fat is not the main determinant of the degree of IR. Other factors, such as fat localization or the degree of inflammation (9,10), may also be relevant.…”

“…Gestation coexists with a state of generalized mild chronic inflammation, which is characterized by increased levels of circulating inflammatory cytokines, and locally by an increase in infiltration of macrophages into adipose tissue (9,10,(36)(37)(38). The inflammatory process is physiological at the end of normal pregnancy (36); however, it is pathological in pregnancy associated with obesity and GDM (10,37).…”

Tumor Necrosis Factor-Induced Cerebral Insulin Resistance in Alzheimer's Disease Links Numerous Treatment Rationales

“…Insulin resistance, commonly a TNF-induced state, and now regarded to be central to AD (see section V.B), is routinely seen in late pregnancy (Ryan et al, 1985). Late pregnancy is also a time of physiological low-grade inflammation (de Castro et al, 2011) that is plausibly regulated by the interactions of gonadotropins and TNF.…”

High levels of chorionic gonadotrophin attenuate insulin sensitivity and promote inflammation in adipocytes

“…Results of previous studies indicated that moderate inflammation during pregnancy is correlated with IR and GDM (Wolf et al 2004, Kinalski et al 2005, de Castro et al 2011.…”