Metabolic flexibility is impaired in women who are pregnant and overweight/obese and related to insulin resistance and inflammation

Context: Maternal obesity is a significant public health concern that contributes to unfavorable outcomes such as inflammation and insulin resistance. Women with obesity may have impaired metabolic flexibility (i.e. an inability to adjust substrate metabolism according to fuel availability). Impaired metabolic flexibility during pregnancy may mediate poor pregnancy outcomes in women with obesity.

Purpose: The purposes of this study were to: 1) compare metabolic flexibility between overweight/obese and lean women; and 2) determine the relationships between metabolic flexibility, inflammation following a high-fat meal, and maternal metabolic health outcomes (i.e. gestational weight gain and insulin resistance).

Procedures: This interventional physiology study assessed lipid oxidation rates via indirect calorimetry before and after consumption of a high-fat meal. The percent change in lipid metabolism was calculated to determine 'metabolic flexibility.' Maternal inflammatory profiles (CRP, IL-6, IL-8, IL-10, IL-12, TNF-α) and insulin resistance (HOMA-IR) were determined via plasma analyses.

Main findings: 64 women who were pregnant (lean = 35, overweight/obese = 29) participated between 32 and 38 weeks gestation. Lean women had significantly higher metabolic flexibility compared to overweight/obese women (lean 48.0 ± 34.1% vs overweight/obese 29.3 ± 34.3%, p = .035). Even when controlling for pre-pregnancy BMI, there was a negative relationship between metabolic flexibility and percent change in CRP among the overweight/obese group (r = -0.526, p = .017). Metabolic flexibility (per kg fat free mass) was negatively correlated with postprandial HOMA-IR (2 h: r = -0.325, p = .016; 4 h: r = -0.319, p = .019).

Conclusions: Overweight and obese women who are pregnant are less 'metabolically flexible' than lean women, and this is related to postprandial inflammation and insulin resistance.