Impact of maternal western diet-induced obesity on offspring mortality and peripheral endocannabinoid system in mice

Abstract

Over two-thirds of adults in the United States are obese or overweight, which is largely due to chronic overconsumption of diets high in fats and sugars (i.e., Western diet). Recent studies reveal that maternal obesity may predispose offspring to development of obesity and other metabolic diseases; however, the molecular underpinnings of these outcomes are largely unknown. The endocannabinoid system is an important signaling pathway that controls feeding behavior and energy homeostasis, and its activity becomes upregulated in the upper small intestinal epithelium of Western diet-induced obese mice, which drives overeating. In the current investigation, we examined the impact of chronic maternal consumption of Western diet on the expression and function of the endocannabinoid system in several peripheral organs important for food intake and energy homeostasis in offspring. Female C57BL/6Tac mice were fed a Western diet or low-fat/no-sucrose control chow for 10 weeks, then males were introduced for mating. Dams were maintained on their respective diets through weaning of pups, at which time pups were maintained on low-fat/no-sucrose chow for 10 weeks. Neonates born from dams fed Western diet, when compared to those born from mice fed control chow, unexpectedly displayed increases in mortality that occurred exclusively within six days following birth (greater than 50% mortality). Males comprised a larger fraction of surviving offspring from obese dams. Furthermore, surviving offspring displayed transient increases in body mass for first two days post weaning, and no marked changes in feeding patterns and endocannabinoid levels in upper small intestinal epithelium, pancreas, and plasma, or in expression of key endocannabinoid system genes in the upper small intestinal epithelium and pancreas at 10 weeks post-weaning. Collectively, these results suggest that maternal diet composition greatly influences survival of neonate C57BL/6Tac mice, and that surviving offspring from dams chronically fed a Western diet do not display marked changes in body mass, eating patterns, or expression and function of the endocannabinoid system in several peripheral organs important for feeding behavior and energy homeostasis.

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring

“…We also did not observe any added adverse metabolic disturbance from HFCO compared to the control NFCO offspring. The discrepancy between our findings and previous study results may be due to the 60% kcal fat diet that we used in the current study compared to the 45% kcal HF diet and Western-style Diet with added cholesterol used in other maternal HF feeding studies [48][49][50][51]53]. The 60% kcal HF diet has more fat but less carbohydrate (20% versus 30-50% kcal in the form of sucrose or fructose) than those diets [54,55].…”

Linoleic acid in diets of mice increases total endocannabinoid levels in bowel and liver: modification by dietary glucose

“…This discrepancy could be because the diet used in our study resulted in 49% of the energy content being from fat as opposed to the more usual 35% reported in the literature (14). Plasma EC levels are very similar to the values reported with consumption of western diets (44). EC levels in duodenum have not previously been reported in LA diets for comparison.…”

Cannabinoid CB1 Receptors Inhibit Gut-Brain Satiation Signaling in Diet-Induced Obesity

“…The latter suggests possible post-transcriptional and/or post-translational changes in expression of these enzymes in the upper small-intestinal epithelium in WD mice when compared to lean SD mice, although this hypothesis remains to be directly tested. Furthermore, a lack of expression of the fatty acid ethanolamide (FAE) biosynthetic enzyme, NAPE-PLD, in CCK-containing cells suggests that FAEs including anandamide—which is also found in small intestinal epithelium of rodents (Izzo et al., 2009; DiPatrizio et al., 2011, 2013, 2015; Argueta and DiPatrizio, 2017; Perez and DiPatrizio, 2018)—is generated in neighboring cells and therefore may act in a paracrine manner with I-cells that contain CB 1 Rs. In contrast, expression of mRNA for the beta isoform of the monoacylglycerol biosynthetic enzyme, DGL, is abundantly expressed in CCK-containing cells, which suggests that 2-AG may signal at CB 1 Rs in an autocrine manner at these cells.…”