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

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 144
Author(s):  
Hunter W. Korsmo ◽  
Kaydine Edwards ◽  
Bhoomi Dave ◽  
Chauntelle Jack-Roberts ◽  
Huanling Yu ◽  
...  

Maternal obesity increases the risk of metabolic dysregulation in rodent offspring, especially when offspring are exposed to a high-fat (HF), obesogenic diet later in life. We previously demonstrated that maternal choline supplementation (MCS) in HF-fed mouse dams during gestation prevents fetal overgrowth and excess adiposity. In this study, we examined the long-term metabolic influence of MCS. C57BL/6J mice were fed a HF diet with or without choline supplementation prior to and during gestation. After weaning, their pups were exposed to either a HF or control diet for 6 weeks before measurements. Prenatal and post-weaning dietary treatments led to sexually dimorphic responses. In male offspring, while post-weaning HF led to impaired fasting glucose and worse glucose tolerance (p < 0.05), MCS in HF dams (HFCS) attenuated these changes. HFCS (versus maternal normal fat control) appeared to improve metabolic functioning of visceral adipose tissue during post-weaning HF feeding, preventing the elevation in leptin and increasing (p < 0.05) mRNA expression of insulin receptor substrate 1 (Irs1) that promotes peripheral insulin signaling in male offspring. In contrast, MCS had minimal effects on metabolic outcomes of female offspring. In conclusion, MCS during HF feeding in mice improves long-term blood glucose homeostasis in male offspring when they are faced with a postnatal obesogenic environment.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hunter Korsmo ◽  
Kaydine Edwards ◽  
Bhoomi Dave ◽  
Chauntelle Jack-Roberts ◽  
Xinyin Jiang

Abstract Objectives Using a mouse gestational diabetes mellitus (GDM) model, this study investigated whether maternal choline supplementation (MCS) could alter postnatal growth and metabolic abnormalities associated with GDM. Methods C57BL/6 mice were either fed a low fat (LF, 10kcal % fat) control diet or a high fat (HF, 60kcal % fat) diet prior to and during pregnancy to induce GDM. These mice received either 25mM choline (MCS) or plain drinking water, After weaning, offspring were fed the HF diet for 6 weeks before glucose tolerance testing and dissection. Results In male offspring from MCS-GDM mothers, we observed a decrease in fasting blood glucose levels and an increase in glucose tolerance when comparing to other groups (P < 0.05). Liver choline metabolite measurements demonstrated that free choline content was lower (P = 0.01) in the MCS-GDM male offspring than control GDM male offspring; there is also an increase in liver sphingomyelin concentrations (P = 0.007) in female offspring from MCS-GDM compared to control GDM dams. Conclusions MCS during GDM leads to improvements in blood glucose control in male mouse offspring exposed to a postnatal HF environment. Funding Sources NIGMS and NIDDK; New York Academy of Sciences.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1022-1022
Author(s):  
Hunter Korsmo ◽  
Moshe Dembitzer ◽  
Sarah Khaldi ◽  
Shameera Sheeraz ◽  
Juliet Kosichenko ◽  
...  

Abstract Objectives This study investigated whether maternal choline supplementation (MCS) could reduce the chronic metabolic stress that is induced by prenatal maternal obesity and postnatal Western Diet (WD) feeding. Methods C57BL/6 dams were either fed a normal fat (NF, 10 kcal %fat) control diet or a high fat (HF, 45 kcal % fat) diet prior to, during pregnancy and during lactation. These dams received either 25 mM choline or plain drinking water. After weaning, offspring were fed the WD diet (45 kcal %fat, 34 kcal %fructose, and 0.25% cholesterol) for 16 weeks before glucose tolerance testing and dissection. Results After 16 weeks of WD feeding, offspring from normal-fat, choline supplemented fed (MCS-NF) dams are protected from weight gain compared to offspring from dams fed a high-fat diet with or without choline supplementation (MCS-HF or MCO-HF)(P &lt; 0.043). Male offspring from MCS-NF fed dams have reduced caloric intake (P &lt; 0.019) and reduced gene expression of Acc1 which mediates liver de novo fatty acid synthesis (P = 0.005) compared to the non-supplemented normal-fat dams (MCO-NF) after 16 weeks of WD feeding. Female offspring from MCS-HF fed dams have lower fasting glucose levels compared to MCO-HF fed dams after 16 weeks of WD feeding (P = 0.034). Conclusions MCS mitigates some pathological hallmarks that are induced by prolonged WD feeding in offspring. Funding Sources NIGMS.


Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 948 ◽  
Author(s):  
Polina E. Panchenko ◽  
Marie-Christine Lacroix ◽  
Mélanie Jouin ◽  
Sarah Voisin ◽  
Karine Badonnel ◽  
...  

According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours.


2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Linh V Nguyen ◽  
Khanh V Doan ◽  

Maternal obesity/diabetes severely affects the offspring’s metabolism not only during the fetal and early life development but also later on in the childhood and adulthood stages. Recent evidence suggested that maternal metformin treatment during pregnancy and breastfeeding might provide long-term metabolic benefits on offspring’s glucose homeostasis. We employed a mouse model of maternal overnutrition induced by high fat diet (HFD) to investigate whether an early metformin treatment in mouse dams during lactation period attenuates the maternal HFD-induced metabolic complications in male offspring. The results showed that male offspring from metformin-exposed mothers during suckling period displayed lower body weight and decreased white fat contents. Furthermore, these male offspring had lower blood glucose levels, decreased hyperinsulinemia, enhanced glucose tolerance and insulin sensitivity. Moreover, we found that short-term metformin treatment during lactation period in mouse dams solely improved the glucose tolerance of male offspring exposed with high fat diet (HFD) during both in utero and early postnatal stages, which might primarily result from an increase in insulin secretion. However, this metformin treatment in mouse dams was enabled to abolish most of the metabolic complications of the male offspring exposed with HFD during lactation period. Together, these findings suggest that an early intervention in mouse dams by metformin treatment during lactation period may provide long-term metabolic benefits in regulation of male offspring’s glucose homeostasis.


2020 ◽  
Vol 103 (4) ◽  
pp. 736-749
Author(s):  
Aridany Suarez-Trujillo ◽  
Katelyn Huff ◽  
Christina Ramires Ferreira ◽  
Tiago Jose Paschoal Sobreira ◽  
Kimberly K Buhman ◽  
...  

Abstract Maternal obesity increases the risk of offspring to become obese and develop related pathologies. Exposure to maternal high-fat diet (HFD) only during lactation increases the risk of obesity-related diseases, suggesting that factors in milk affect long-term health. We hypothesized that prepregnancy obesity induced by HFD alters milk lipidome, and in turn, alterations may affect neonate serum lipidome. The objective of this study was to determine the effect of prepregnancy obesity induced by HFD on circulating lipids in dams and neonates and in milk. Female mice were fed an HFD (60% kcal fat) or control diet (CON, 10% kcal fat) beginning 4 weeks before breeding. On postnatal day 2 (PND2), pups were cross-fostered to create pup groups exposed to HFD during pregnancy, lactation, or both or exposed to CON. On PND12, dams were milked and then euthanized along with pups to collect blood. Serum and milk were processed for multiple reaction monitoring (MRM) lipidomics profiling to quantify the relative expression of lipid classes. Lipidome of HFD dam serum and milk had increased proportion of C18:2 free fatty acid and fatty acyl residues in all lipid classes. Lipidome of serum from pups exposed to maternal HFD during lactation was similarly affected. Thus, maternal HFD induced redistribution of fatty acyl residues in the dam’s circulation, which was associated with modification in milk and suckling neonate’s lipidome. Further studies are needed to determine if increased circulating levels of C18:2 in neonate affects development and predisposes offspring to obesity and metabolic syndrome.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 757
Author(s):  
Jennifer M. Monk ◽  
Wenqing Wu ◽  
Dion Lepp ◽  
K. Peter Pauls ◽  
Lindsay E. Robinson ◽  
...  

Cooked common beans (Phaseolus vulgaris) improve intestinal health in lean mice and attenuate intestinal dysbiosis and inflammation when consumed concurrent with obesity development. We determined the effects of a high-fat (HF) bean supplemented diet in mice with established obesity (induced by 12 weeks of HF diet (60% fat as kcal)) compared to obese mice consuming a HF or low-fat (LF) weight loss control diet. Obese C57BL/6 male mice remained consuming HF for eight weeks or were randomly switched from HF to an isocaloric HF with 15.7% cooked navy bean powder diet (HFàHFB) or LF (11% fat as kcal; HFàLF) (n = 12/group). HFàHFB improved the obese phenotype, including (i) fecal microbiome (increased Prevotella, Akkermansia muciniphila, and short-chain fatty acid levels), (ii) intestinal health (increased ZO-1, claudin-2, Muc2, Relmβ, and Reg3γ expression), and (iii) reduced adipose tissue (AT) inflammatory proteins (NFκBp65, STAT3, IL-6, MCP-1, and MIP-1α), versus HF (p < 0.05). Conversely, HFàLF reduced body weight and circulating hormones (leptin, resistin, and PAI-1) versus HF and HFàHFB (p < 0.05); however, AT inflammation and intestinal health markers were not improved to the same degree as HFàHFB (p < 0.05). Despite remaining on a HF obesogenic diet, introducing beans in established obesity improved the obese phenotype (intestinal health and adipose inflammation) more substantially than weight loss alone.


Diabetes ◽  
1996 ◽  
Vol 45 (9) ◽  
pp. 1253-1258 ◽  
Author(s):  
K. J. Jensen-Urstad ◽  
P. G. Reichard ◽  
J. S. Rosfors ◽  
L. E. L. Lindblad ◽  
M. T. Jensen-Urstad

2007 ◽  
Vol 292 (5) ◽  
pp. R1810-R1818 ◽  
Author(s):  
Claire J. Stocker ◽  
Ed Wargent ◽  
Jacqueline O'Dowd ◽  
Claire Cornick ◽  
John R. Speakman ◽  
...  

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg·kg−1·day−1) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
E. Chang ◽  
H. Hafner ◽  
M. Varghese ◽  
C. Griffin ◽  
J. Clemente ◽  
...  

Abstract With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.


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