Maternal Choline and Betaine Supplementation Modifies the Placental Response to Hyperglycemia in Mice and Human Trophoblasts

Nanobashvili, Khatia; Jack-Roberts, Chauntelle; Bretter, Rachel; Jones, Naudia; Axen, Kenneth; Saxena, Anjana; Blain, Kali; Jiang, Xinyin

doi:10.3390/nu10101507

Cited by 16 publications

(10 citation statements)

References 50 publications

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“…Vitamin C, a famous antioxidant which exists mainly in cytosol, has been proved to inhibit in the physiological production of other antioxidants such as superoxide dismutase-1 and glutathione peroxidase-1, leading to the increased ROS production. 28,29 Of note, after long-time exposure to AX in SM cells, the inhibitory effects mentioned above were not observed (data not shown) probably because of its specialty in either localization or action. Although this evidence is far from enough and more various signaling are required to explore, AX seems to have less side effect and less impact on positive physiological cellular function.…”

Section: Discussionmentioning

confidence: 91%

Effects of Astaxanthin on Inflammation and Insulin Resistance in a Mouse Model of Gestational Diabetes Mellitus

et al. 2020

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Gestational diabetes mellitus (GDM) is a condition in which a hormone made by the placenta prevents the body from using insulin effectively. It is important to find an effective treatment. A mouse model of GDM was used to testify the effects of astaxanthin on glucose tolerance and insulin sensitivity. Production of inflammatory cytokines, reactive oxygen species (ROS), and glucose transporter type 4 (GLUT4) translocation and insulin-related signaling were measured in the presence of astaxanthin both in vivo and in vitro. It was found that astaxanthin improved insulin sensitivity, glucose tolerance, and litter size of offspring and reduced birth weight of offspring and inflammation in GDM mouse. Moreover, astaxanthin increased GLUT4 translocating to membrane without altering its secretion/expression and glucose uptake and consumption in C2C12 skeletal muscle cells. Furthermore, ROS generation and insulin-related signaling inhibited by tumor necrosis factor α was restored by astaxanthin. It is concluded that astaxanthin has the potential to attenuate GDM symptoms by regulating inflammation and insulin resistance in skeletal muscle of pregnant mice. Our findings suggest that astaxanthin could be a promising and effective molecule to treat GDM.

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Section: Discussionmentioning

confidence: 91%

Effects of Astaxanthin on Inflammation and Insulin Resistance in a Mouse Model of Gestational Diabetes Mellitus

et al. 2020

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“…As the supply of methyl groups is vital during pregnancy, we speculate that high levels of betaine protect the fetuses in pregnant bears during hibernation. Indeed, betaine plays an important role in physiologic pregnancy 58 , fetal development 59,60 and DNA methylation 61 . Furthermore, in dairy cattle, betaine supplementation increase lactation performance 62 .…”

Section: Discussionmentioning

confidence: 99%

Insights in the regulation of trimetylamine N-oxide production using a comparative biomimetic approach suggest a metabolic switch in hibernating bears

Ebert

Painer

Bergman

et al. 2020

Sci Rep

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Experimental studies suggest involvement of trimethylamine N-oxide (TMAO) in the aetiology of cardiometabolic diseases and chronic kidney disease (CKD), in part via metabolism of ingested food. Using a comparative biomimetic approach, we have investigated circulating levels of the gut metabolites betaine, choline, and TMAO in human CKD, across animal species as well as during hibernation in two animal species. Betaine, choline, and TMAO levels were associated with renal function in humans and differed significantly across animal species. Free-ranging brown bears showed a distinct regulation pattern with an increase in betaine (422%) and choline (18%) levels during hibernation, but exhibited undetectable levels of TMAO. Free-ranging brown bears had higher betaine, lower choline, and undetectable TMAO levels compared to captive brown bears. Endogenously produced betaine may protect bears and garden dormice during the vulnerable hibernating period. Carnivorous eating habits are linked to TMAO levels in the animal kingdom. Captivity may alter the microbiota and cause a subsequent increase of TMAO production. Since free-ranging bears seems to turn on a metabolic switch that shunts choline to generate betaine instead of TMAO, characterisation and understanding of such an adaptive switch could hold clues for novel treatment options in burden of lifestyle diseases, such as CKD.

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“…water available ad libitum. The GDM model was established by being fed with high-fat diet (HFD; 60% kcal from fat) for 4 wk before pregnancy 12,13 . The pregnant mice were obtained by proesterous normal females being left for one night to copulate with the normal males (2:1).…”

Section: Methodsmentioning

confidence: 99%

GDM progenies exhibit sex disparity in metabolism after respective therapies of insulin, glibenclamide and metformin in dams during pregnancy

Jjang

Jia

et al. 2020

Preprint

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Background： The drug treatments for the pregnant women with gestational diabetes mellitus (GDM) have been concerned with their effects on both mothers and offspring. The aim of this study was to compare the intergenerational effects of insulin, glibenclamide and metformin on glucose and lipid metabolism in the offspring born to GDM mice. Methods: The murine GDM was induced by high fat diet. The offspring were grouped based on the treatments in maternal mice. ITT and GTT were performed at 4th week and 8th week of age, respectively. Serum levels of TC, TG, HDL-C and LDL-C plus hepatic levels of TG and TC, were respectively determined by enzymatic kits. Western blotting was conducted to detect related proteins in the livers from offspring. Results: The normalization of the dyslipidemia, hepatic lipid abnormality and insulin insensitivity elicited by the respective therapies of insulin, glibenclamide and metformin during maternal pregnancy still persisted in the male adult offspring. Specifically, the decreases in plasma TC, TG, LDL-C levels (29%, 37.8% and 57.7%, respectively, p˂0.05) and hepatic lipid contents (TC 31.3% and TG 39.2%, p˂0.05), the increases in hepatic phosphorylation levels of AKT, CPT1A ,PPAR- α and PPAR-γ (57.1%, 91.7% , 68% and 173.3%, respectively, p˂0.05) and the inhibition of G6Pase, PEPCK, HMGCS1 (35.7%, 68.8% and 77.3% respectively, p˂0.05) were still observed in the male offspring born to treated GDM mice from 4th to 8th week of age. Unexpectedly, the female progeny born to untreated GDM mice showed an autonomous recovery in glucose and lipid metabolism. Conclusions: Respective treatments in GDM mice during pregnancy with insulin, glibenclamide and metformin have the long-term persisted effects in male offspring, while female progenies born to untreated dams showed an autonomous inhibition of intergenerational relay of glucose and lipid dysregulation. Our current findings may shed a new light into GDM clinical practice.

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Maternal Choline and Betaine Supplementation Modifies the Placental Response to Hyperglycemia in Mice and Human Trophoblasts

Cited by 16 publications

References 50 publications

Effects of Astaxanthin on Inflammation and Insulin Resistance in a Mouse Model of Gestational Diabetes Mellitus

Effects of Astaxanthin on Inflammation and Insulin Resistance in a Mouse Model of Gestational Diabetes Mellitus

Insights in the regulation of trimetylamine N-oxide production using a comparative biomimetic approach suggest a metabolic switch in hibernating bears

GDM progenies exhibit sex disparity in metabolism after respective therapies of insulin, glibenclamide and metformin in dams during pregnancy

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