Maternal and Postnatal Overnutrition Differentially Impact Appetite Regulators and Fuel Metabolism

Abstract

Maternal obesity is increasing, and it is known that the intrauterine experience programs fetal and newborn metabolism. However, the relative contributions of pre- or postnatal factors are unknown. We hypothesized that maternal overnutrition caused by long-term maternal obesity would exert a stronger detrimental impact than postnatal overnutrition on offspring metabolic homeostasis, with additional postnatal overnutrition exaggerating these alterations. Female Sprague Dawley rats were exposed to chow or high-fat cafeteria diet for 5 wk before mating and throughout gestation and lactation. On postnatal d 1, litters were adjusted to three per litter to induce postnatal overnutrition (vs. 12 in control). Hypothalamic appetite regulators neuropeptide Y and proopiomelanocortin, glucose transporter 4, and lipid metabolic markers were measured. At postnatal d 20, male pups born of obese dams, or those overnourished postnatally, were 42% heavier than controls; combining both interventions led to 80% greater body weight. Maternal obesity increased pup adiposity and led to glucose intolerance in offspring; these were exaggerated by additional postnatal overnutrition during lactation. Maternal obesity was also linked to hyperlipidemia in offspring and reduced hypothalamic neuropeptide Y and increased proopiomelanocortin mRNA expression. Postnatal overnutrition of offspring from obese dams amplified these hypothalamic changes. Both maternal and postnatal overnutrition reduced muscle glucose transporter 4. Adipose carnitine palmitoyl-transferase-1 and adipose triglyceride lipase mRNA was up-regulated only by postnatal overnutrition. Maternal overnutrition appears to alter central appetite circuits and promotes early-onset obesity; postnatal overnutrition interacted to cause peripheral lipid and glucose metabolic disorders, supporting the critical message to reduce early-life adverse nutritional impact.

Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions

“…Data has predominantly come from studies that use a combined high-sugar/high-fat palatable obesogenic diet. 33,[40][41][42][43][44] Consistently, a hyperphagic phenotype is identified, in particular in male offspring. Although early data suggested that the hyperphagic behaviour was isolated to junk food in preference to chow, 40 more recent data has demonstrated that the overeating phenotype is also observed in chow-fed offspring of obese mothers.…”

Delayed introduction of solid feeding reduces child overweight and obesity at 10 years

“…Animal models of alterations to early life feeding clearly show sustained changes in appetite setting and defended weight trajectory. 28,29 Early life may provide a time period for truly effective preventative interventions. 30 Antenatal parental smoking was strongly associated with the above healthy BMI in childhood in this cohort, independent of socioeconomic factors and feeding practices.…”

Exposure to a High-Fat Diet During Development Alters Leptin and Ghrelin Sensitivity and Elevates Renal Sympathetic Nerve Activity and Arterial Pressure in Rabbits

“…9 Possible mechanisms include reduced hypothalamic STAT-3 (signal transducer and activator of transcription 3) phosphorylation 24 or increased levels of the orexigenic neuropeptide Y in offspring, together with reduced levels of POMC (pro-opiomelanocortin). 25 Hence, alterations in the levels of these neuropeptides may affect appetite and sympathetic activation in offspring from mothers fed an HFD and may explain the greater pressor and sympathetic responses to leptin observed in m-HFD rabbits compared with m-NFD rabbits.…”