Obesity and exposure to light at night are prevalent in modern society and associated with changes in physiology and behavior that can affect a female's ability to support offspring growth during pregnancy and lactation. A 2X3 factor study of ICR mice was conducted to determine the effect of diet [control (CON; 10% fat) or high fat (HF; 60% fat)] and exposure to regular 12 h light:dark cycles (LD) or continuous low (L5) or high (L100) lux of light on gestation length, birth litter size, milk composition and litter growth to lactation day 12. HF diet reduced birth litter size, but increased postnatal d 12 litter weight (P<0.05), whereas constant light tended to increase litter weight (P=0.07). Continuous light increased gestation length, altered dam feed intake, increased serum prolactin and increased final dam and mammary gland weight (P<0.05), while decreasing mammary ATP content and milk lactose (P<0.05). Correlation analysis indicated a positive relationship between final litter weight and mammary size, metabolic stores (e.g. maternal fat pad weight), kcal of feed intake, and gestation length (P<0.05). Although CON mice spent more time eating than HF dams, the calorically dense HF diet was related to greater rates of litter growth to peak lactation. Constant light circadian disrupting effects appear to be confounded by a potential long day photoperiod response exemplified by higher circulating levels of prolactin and increased body and mammary weight of females exposed to these conditions. Other model systems may be better to study the interacting effects of obesity and circadian disruption on reproductive competence.

This study’s objective was to determine the effects of pre-pregnancy obesity induced by a high-fat diet and exposure to circadian-disrupting light-dark phase shifts on birth littler size, pup survival to 24h and growth to lactation day 12, and their relationship to maternal feeding patterns, fecal corticosterone levels, milk composition, and lipid profiles of liver, plasma, mammary gland, and milk. A 2 by 2 factorial designed experiment of female ICR mice assigned to control (CON; 10% fat) or high-fat (HF; 60% fat) and either a 12-hour light-dark (LD) cycle or a chronic jet lag model of 6-hour phase-shifts (PS) in light-dark cycle every 3 days throughout pregnancy and lactation, resulted in 4 treatment groups: CON-LD, CON-PS, HF-LD and HF-PS. HF diet increased maternal pre-pregnancy body weight and elevated milk lactose. Whereas PS reduced milk lactose within the CON diet group, and increased maternal feed intake and fecal corticosterone levels. PS exposure also affected the time of day of birth. Neither PS nor HF affected birth litter size or pup survival. Only diet impacted final litter weight, with HF greater than CON. Among the 1204 lipids detected by multiple reaction monitoring (MRM)-profiling, diet altered 67.1% in milk, 58.1% in mammary gland, 27.2% in the liver, and 10.9% in plasma, with HF increasing the carbon length of diacylglycerols in the liver and milk, and carbon length of triacylglycerols in plasma, mammary gland and milk. Although exposure to PS had no overall impact on maternal lipid profiles, interactions (P < 0.05) were found between PS and diets in the phosphatidylcholine and phosphatidylethanolanine class of lipids. Findings support that high fat diet and exposure to circadian disrupting environments impact maternal feeding behavior and stress responses as well as lipid profiles, which may relate to their negative association with maternal health and offspring development.

The prevalence of constant light exposure and high-fat diet in modern society raises concerns regarding their impact on maternal and offspring health outcomes. In rodents, exposure to maternal high-fat diet or continuous light negatively program metabolic and stress response outcomes of offspring. A 2x3 factorial study was conducted to investigate the impact of diet (control–CON, 10% fat, or high fat–HF, 60% fat) and exposure to different lighting conditions: regular 12-hour light-dark cycles (LD), continuous dim light (L5), or continuous bright light (L100) on female ICR mice daily patterns of time in and out of the nest, feed intake, and fecal corticosterone levels during gestation and lactation. Our previous analysis of these mice found HF diet decreased number of pups born, but increased litter growth rate to postnatal (PN) d12. Whereas continuous light increased gestation length and tended to increase PN litter growth. Here we report that patterns of grams of feed intake, an indicator of feeding activity, were affected by light, diet, period of the day (day versus night) and physiological state (gestation and lactation), with significant interactions among all these variables (P<0.05). HF diet and light treatment increased fecal corticosterone output (P<0.05) during lactation. Dams exhibited significant 12 h and 24 h rhythms of activity out of the nest in the first 48 h postnatal, with time outside of the nest greater in the second 24 h period. L100 treatment and HF diet attenuated rhythms and shifted phase of rhythms relative to LD and CON, respectively (P<0.05). Alterations in behavior affect maternal physiology, including level and timing of release of corticosteroids. Elevated fecal corticosterone levels due to high-fat diet and continuous light may have potential implications on maternal-offspring health, and potentially underlie some of the adverse effects of modern lifestyle factors on maternal and offspring health.

Macrophages harness pattern recognition receptors (PRRs) to detect conserved bacterial components and mount effective immune responses. Many Gram-negative bacteria modify their lipid A structures to limit recognition by Toll-like receptor 4 (TLR4) and cytosolic Caspase-11 lipopolysaccharide sensors. One common evasion strategy is to reduce the lipid A acylation state from hexa- to tetra-acylation. This alteration can limit binding to receptors and dampen subsequent immune signaling responses, yet the proteomic alterations associated with this altered immunogenicity remain incompletely understood. Here, we systematically profiled proteomic alterations induced by extracellular or transfected hexa-acylated Kdo2-lipid A (Kdo2) and tetra-acylated lipid-IVa (IVa) to assess TLR4-dependent, TLR4-independent, and non-canonical inflammasome activation pathways. Kdo2 elicited stronger inflammatory responses in immortalized bone-marrow-derived macrophages (iBMDMs), as evidenced by robust TNF production, Caspase-11 cleavage, and IL-1α/IL-1β release. In contrast, IVa elicited minimal TNF secretion and failed to effectively induce non-canonical inflammasome activation. Global label-free quantitative proteomic analysis of iBMDMs stimulated with a low dose of immunogenic LPS displayed route-specific immune signatures: enrichment of TNF signaling, interferon-associated pathways, and mitochondrial metabolic remodeling. Equimolar amounts of low-acylated LPS failed to effectively induce these immune signatures, supporting a threshold-dependent model in which the lipid A structure and route of exposure define inflammatory progression. Collectively, our findings provide mechanistic insight into how lipid A structural variation modulates macrophage immune programming and cytosolic inflammasome activation.