scholarly journals High 5MTHF, but Not Folic Acid During Pregnancy, Alters Hypothalamic Regulatory Pathways and Associates with Post-Partum Weight-Gain in Wistar Rat Mothers

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1230-1230
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Rebecca Simonian ◽  
Zdenka Pausova ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Weight Gain ◽  
Food Intake ◽  
Differentially Expressed Genes ◽  
Hormone Receptor ◽  
Body Weight Gain ◽  
Post Partum ◽  
Wistar Rat ◽  
Regulatory Pathways

Abstract Objectives 5-methyltetrahydrofolate (5MTHF), the bioactive folate form, has been proposed an alternative supplement to folic acid (FA) due to direct cellular uptake and utilization. In North America, 5MTHF is incorporated into prenatal supplements at the equivalent high dose (1000 µg) as FA and discussion has been raised of its formation into baby formula. Our lab was the first to compare the dose (1X vs high, 5X) and form (FA vs 5MTHF) effects of folate during pregnancy on later-life metabolic health of the Wistar rat mother. Contrary to our hypothesis, 5MTHF diets, independent of dose, led to mothers with 40% greater body weight-gain and higher food intake post-birth compared to FA. The objective of this study was to identify differentially expressed genes and related hypothalamic pathways of mothers fed FA vs 5MTHF diets during pregnancy. Methods Pregnant Wistar rats were fed an AIN-93 G diet with recommended (1X, control, 2 mg/kg diet) or high (5X) FA or equimolar levels of 5MTHF. At birth, a subset of dams were terminated and RNA-seq analysis was performed in the arcuate nucleus of the hypothalamus (ARC), a key regulator of body weight and food intake, in dams fed the high FA and MTHF diets. Results Over 350 differentially expressed genes were identified in the ARC of dams fed high 5MTHF vs FA diets. Combining differential gene expression patterns with reported GO function terms and Kegg pathway analyses, four candidate genes (prolactin hormone receptor, corticotropin releasing hormone receptor, KISS1 peptide and dopamine receptor) were validated by qPCR thus far as plausible contributors to higher body weight-gain and food intake in 5MTHF dams. These genes correspond to neuroactive ligand-receptor interaction pathway (path: hsa04080), associated with metabolic diseases including leptin deficiency and genetic obesity. Other significantly enriched pathways included the retrograde endocannabinoid signalling and morphine addiction pathway. Conclusions High 5MTHF supplementation during pregnancy alters expression of central feeding regulatory pathways in the hypothalamus of the mother, potentially programming post-partum body-weight gain. 5MTHF, at the equivalent dose of FA, may not be the preferred folate form during pregnancy. Funding Sources CIHR-INMD; EP supported by NSERC-CGS D.

scholarly journals Choline and Folic Acid Balance in Diets During Pregnancy Programs Food Intake Regulation in Wistar Rat Offspring (FS08-05-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Rola Hammoud ◽  
Chih-Sheng Liao ◽  
Emanuela Pannia ◽  
Mandy Ho ◽  
Neil Yang ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Control Diet ◽  
Wistar Rat ◽  
Rat Offspring ◽  
Food Intake Regulation ◽  
Intake Regulation

Abstract Objectives High gestational folic acid (FA) induces an obesogenic phenotype in male Wistar rat offspring. Imbalances between FA and other methyl-nutrients (i.e., choline) leading to perturbations in the 1-carbon cycle may account for the effects of high FA diets. Canadian women consume high (2–7-fold) intakes of FA, but most are not meeting recommended adequate intakes for choline. Choline is also absent from Canadian prenatal supplements. The objective of this study is to evaluate the effects of the interaction between choline and FA in maternal diets of rats on the 1-carbon cycle, and the programming of food intake, body weight gain and biomarkers of obesity in the offspring later in life. Methods Pregnant Wistar rat dams were fed the AIN-93 G diet with recommended (1X) choline and FA (RCRF, control), or a 5X FA diet with either 0.5X choline (LCHF), 1X choline (RCHF), or 2.5X choline (HCHF). Brain and blood were collected at birth. At weaning one male pup/dam from all groups was maintained on the control diet for 20 weeks then terminated. Dependent measures include weekly body weight-gain and food intake, plasma glucoregulatory hormones and 1-carbon metabolites at birth and post-weaning. Results Increasing choline content to 2.5-fold in a high (5-fold) gestational FA diet (HCHF) led to lower plasma insulin and leptin levels at birth compared to the LCHF and RCHF diets, respectively (P < 0.05). It also led to lower (25%, P = 0.03) plasma 5-methyltetrahydrofolate concentrations at birth compared to the RCHF diet, suggesting more efficient utilization of FA. Offspring born to dams maintained on a high folic acid diet with either low or recommended choline had higher weekly food intake (6%, P < 0.05) and body weight-gain (9%, P < 0.01). In contrast, offspring from dams fed the HCHF gestational diet were not different from those born to dams fed the RCRF (control) diet, highlighting the mitigating effects of a balanced choline and FA gestational diet. Conclusions Increased intakes of choline mitigate the effects of high FA diets. Maternal dietary choline interacts with FA on the long-term programming of food intake regulation in the offspring; emphasizing a need for more attention to improving choline intakes by women of child-bearing age. Funding Sources This research was funded by the Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD).

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

scholarly journals The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2441-2452 ◽  
Author(s):  
Tomokazu Hata ◽  
Noriyuki Miyata ◽  
Shu Takakura ◽  
Kazufumi Yoshihara ◽  
Yasunari Asano ◽  
...  
Keyword(s):  
Body Weight ◽  
Anorexia Nervosa ◽  
Weight Gain ◽  
Food Intake ◽  
Brain Stem ◽  
Body Weight Gain ◽  
Field Tests ◽  
Compulsive Behavior ◽  
The Brain ◽  
Poor Weight Gain

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.

Bimatoprost promotes satiety and attenuates body weight in rats fed standard or obesity-promoting diets.

2020 ◽  
Author(s):  
Clayton Spada ◽  
Chau Vu ◽  
Iona Raymond ◽  
Warren Tong ◽  
Chia-Lin Chuang ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Gastric Emptying ◽  
Food Intake ◽  
Visceral Fat ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Sprague Dawley ◽  
Hormone Levels ◽  
Gut Hormone

Abstract Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.

scholarly journals Oxytocin Administration Alleviates Acute but Not Chronic Leptin Resistance of Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 88 ◽  
Author(s):  
Mehdi Labyb ◽  
Chloé Chrétien ◽  
Aurélie Caillon ◽  
Françoise Rohner-Jeanrenaud ◽  
Jordi Altirriba
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Leptin Resistance ◽  
Obese Mice ◽  
Short Term ◽  
Continuous Administration ◽  
Pre Treatment ◽  
Treatment Of Obesity

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.

scholarly journals Effects of Consuming Sugar-Sweetened Beverages for 2 Weeks on 24-h Circulating Leptin Profiles, Ad Libitum Food Intake and Body Weight in Young Adults

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3893 ◽  
Author(s):  
Desiree M. Sigala ◽  
Adrianne M. Widaman ◽  
Bettina Hieronimus ◽  
Marinelle V. Nunez ◽  
Vivien Lee ◽  
...  
Keyword(s):  
Young Adults ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Energy Intake ◽  
Body Weight Gain ◽  
Energy Requirement ◽  
Area Under The Curve ◽  
Sugar Sweetened Beverage ◽  
Ad Libitum

Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18–35 kg/m2; 18–40 years) consumed three beverages/day containing aspartame or 25% energy requirement as glucose, fructose, high fructose corn syrup (HFCS) or sucrose (n = 23–28/group). Body weight, ad libitum food intake and 24-h leptin area under the curve (AUC) were assessed at Week 0 and at the end of Week 2. The Δbody weight was not different among groups (p = 0.092), but the increases in subjects consuming HFCS- (p = 0.0008) and glucose-SB (p = 0.018) were significant compared with Week 0. Subjects consuming sucrose- (+14%, p < 0.0015), fructose- (+9%, p = 0.015) and HFCS-SB (+8%, p = 0.017) increased energy intake during the ad libitum food intake trial compared with subjects consuming aspartame-SB (−4%, p = 0.0037, effect of SB). Fructose-SB decreased (−14 ng/mL × 24 h, p = 0.0006) and sucrose-SB increased (+25 ng/mL × 24 h, p = 0.025 vs. Week 0; p = 0.0008 vs. fructose-SB) 24-h leptin AUC. The Δad libitum food intake and Δbody weight were not influenced by circulating leptin in young adults consuming sugar-SB for 2 weeks. Studies are needed to determine the mechanisms mediating increased energy intake in subjects consuming sugar-SB.

scholarly journals Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats

Life Sciences ◽  
2007 ◽  
Vol 81 (12) ◽  
pp. 1024-1030 ◽  
Author(s):  
SuJean Choi ◽  
Briana DiSilvio ◽  
JayLynn Unangst ◽  
John D. Fernstrom
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Chronic Infusion

Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone

1993 ◽  
Vol 264 (6) ◽  
pp. E986-E992 ◽  
Author(s):  
J. C. Byatt ◽  
N. R. Staten ◽  
W. J. Salsgiver ◽  
J. G. Kostelc ◽  
R. J. Collier
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Mature Female ◽  
Female Rats ◽  
Bovine Growth Hormone ◽  
Female Rat ◽  
Moisture Percentage

Recombinant bovine prolactin (rbPRL) or bovine growth hormone (rbGH) was administered to mature female rats (10/treatment group) by daily subcutaneous injection for 10 days. Doses ranged from 7 to 5,000 micrograms/day (0.03-24 mg/kg body wt). Both rbPRL and rbGH increased body weight gain and food intake, but these parameters were increased at lower doses of rbPRL (7-63 micrograms/day) than rbGH (> 190 micrograms/day). Weight gain and food intake were maximally stimulated by 190 micrograms/day rbPRL, whereas maximal increased weight gain was obtained with the highest dose of rbGH (5,000 micrograms/day). Total carcass protein was increased by both hormones; however, protein as a percentage of body weight was unchanged. Similarly, neither rbPRL nor rbGH changed the percentage of carcass moisture. Percentage of body fat was increased by rbPRL but was decreased by rbGH. Weight of the gastrointestinal tract and kidneys was increased by both hormones, but increases were in proportion to body weight gain. These data confirm that ungulate prolactin is a hyperphagic agent in the female rat. In addition, they suggest that, while prolactin stimulates growth in mature female rats, this growth is probably not via a somatogenic mechanism.

Capsaicin-sensitive fibers are required for the anorexic action of systemic but not central bombesin

1999 ◽  
Vol 276 (6) ◽  
pp. R1617-R1622 ◽  
Author(s):  
David Michaud ◽  
Hymie Anisman ◽  
Zul Merali
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Neural Circuits ◽  
Body Weight Gain ◽  
Systemic Effects ◽  
Neuronal System ◽  
Afferent Neurons ◽  
The Brain

Bombesin (BN) suppresses food intake in rats whether given centrally or systemically. Although the brain BN-sensitive receptors are known to be essential for the anorexic effect of systemic BN, the mode of communication between the gut and the brain remains unclear. This study assessed whether the anorexic effect of systemic BN is mediated humorally or via neural circuits. Afferent neurons were lesioned using capsaicin (50 mg/kg sc) on postnatal day 2, and responses to BN were assessed during adulthood. Capsaicin treatment decreased body weight gain significantly from postnatal age 4–7 wk. Peripheral BN (4–16 μg/kg ip) dose dependently suppressed food intake in control animals. However, this effect was completely blocked in capsaicin-treated rats. In contrast to systemic effects, feeding-suppressant effects of centrally administered BN (0.01–0.5 μg icv) were not affected by capsaicin treatment. This research suggests that peripheral BN communicates with the brain via a neuronal system(s) whose afferent arm is constituted of capsaicin-sensitive C and/or Aδ-fibers, whereas the efferent arm of this satiety- and/or anorexia-mediating circuitry is capsaicin resistant.

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