Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity

Abstract

IntroductionThe implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed.MethodsHere we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats.ResultsWe have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1β in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to in utero neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes.DiscussionTogether, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.

Identifying of immune‐associated genes for assessing the obesity‐associated risk to the offspring in maternal obesity: A bioinformatics and machine learning

“…The perinatal obesogenic milieu of maternal obesity leads to hypothalamic inflammation, which is a crucial mechanism for metabolic dysregulation in offspring 10 . Alleviating hypothalamic inflammation with cannabidiol significantly enhanced the peripheral metabolic profile of Wistar rat offspring 32 . A prospective human dual‐cohort study observed an approximately linear association between maternal pre‐pregnancy BMI and offspring hypothalamic microstructure on MRI images, further demonstrating the plasticity of prenatal hypothalamic development in the context of maternal overnutrition during pregnancy 33 …”

“…10 Alleviating hypothalamic inflammation with cannabidiol significantly enhanced the peripheral metabolic profile of Wistar rat offspring. 32 A prospective human dual-cohort study observed an approximately linear association between maternal pre-pregnancy BMI and offspring hypothalamic microstructure on MRI images, further demonstrating the plasticity of prenatal hypothalamic development in the context of maternal overnutrition during pregnancy. 33 Interestingly, in the present study, the hypothalamic DEGs of offspring with maternal obesity were not only enriched in the physical functions of the hypothalamus (such as neurodevelopment and metabolic hormone regulation) but also in immune system regulation.…”

Effects of Oral Cannabidiol on Health and Fitness in Healthy Adults: An 8-Week Randomized Trial

“…It is possible that longer observation times and with higher doses of CBD are necessary to induce measurable changes in body composition. It is also possible that the anti-inflammatory effects of CBD which potentially modulate metabolic regulators in muscle are only observable in preclinical studies [ 46 ]. The effect of long-term CBD consumption on LBM and BF% in humans is understudied and is only addressed in survey-based cannabis research.…”