Abstract
Background/objectivesThe murine postnatal leptin surge occurs within the first 4 weeks of life and is critical for neuronal projection development within hypothalamic feeding circuits. Here we describe the influence of nutritional status on the timing and magnitude of the postnatal leptin surge in mice.MethodsPlasma leptin concentrations were measured 1–3 times per week for the first 4 weeks of life in C57BL/6J pups reared in litters adjusted to 3 (small), 7–8 (normal), or 11–12 (large) pups per dam fed breeder chow or raised in litters of 7–8 by dams fed high-fat diet (HFD) ad libitum starting either prior to conception or at parturition.ResultsMice raised in small litters become fatter than pups raised in either normal or large litters. The leptin surge in small litter pups starts earlier, lasts longer, and is dramatically larger in magnitude compared to normal litter pups, even when leptin concentrations are normalized to fat mass. In mice reared in large litters, weight gain is diminished and the surge is both significantly delayed and lower in magnitude compared to control pups. Pups reared by HFD-fed dams (starting preconception or at parturition) are fatter and have augmented leptin surge magnitude compared to pups suckled by chow-fed dams. Surge timing varies depending upon nutritional status of the pup; the source of the surge is primarily subcutaneous adipose tissue. At peak leptin surge, within each group, fat mass and plasma leptin are uncorrelated; in comparison with adults, pups overproduce leptin relative to fat mass. Plasma leptin elevation persists longer than previously described; at postnatal day 27 mice continue overproducing leptin relative to fat mass.ConclusionsIn mice, small litter size and maternal HFD feeding during the perinatal period augment the plasma leptin surge whereas large litter size is associated with a delayed surge of reduced magnitude.
Highlights
Obesity is a major public health concern with an alarming obesity prevalence of 38% in US adults and 17% in US youth [1]
Deficiency of leptin during development impairs the formation of projections from the arcuate nucleus of hypothalamus (ARH) to other brain regions involved in energy homeostasis such as the paraventricular nucleus (PVH), the dorsomedial hypothalamic nucleus (DMH), and the lateral hypothalamic area (LHA) [9]
In C57BL/6J mice raised in conventional litters of 7–8 animals, plasma leptin peaks at P10 and remains modestly elevated until P27
Summary
Obesity is a major public health concern with an alarming obesity prevalence of 38% in US adults and 17% in US youth [1]. Maternal HFD feeding during gestation and lactation augments the postnatal leptin surge in the progeny [13, 21, 22]; and maternal caloric restriction reduces body weight of pups and reduces their postnatal leptin surge [14]. [12, 13], and reduced density of α-MSH projections from the ARH to PVH, DMH and LHA in 8-week-old progeny [12] These same projections are disrupted in congenitally leptin deficient mice, suggesting that the effects of nutritional state during the postnatal period on adult body weight may be mediated through effects on the postnatal leptin surge. We determined how the leptin surge is affected by early over- or undernutrition and maternal HFD feeding during the first 4 weeks of life and how it is affected by fat mass of the pup. We conclude that postnatal overfeeding and maternal HFD feeding augment the leptin surge whereas postnatal underfeeding diminishes and delays the surge even when adjusted for the fat mass of pups
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
