scholarly journals Dietary Intakes of Folic Acid During Pregnancy Determines Maternal Re-Set of Metabolism Post-Birth in Wistar Rat Dams (FS08-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Emanuela Pannia ◽  
Neil Yang ◽  
Mandy Ho ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Folic Acid ◽  
Food Intake ◽  
Metabolic Pathways ◽  
Wistar Rat ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Maternal Metabolism ◽  
Carbon Pathways

Abstract Objectives Nutrition during pregnancy alters the “re-set” of maternal metabolism and in turn the mother's metabolic phenotype later in life. Folic acid (FA, synthetic folate) consumed at intakes above requirements during pregnancy by rats leads to increased weight gain and altered DNA methylation in central and peripheral pathways regulating food intake. The objectives of this study were to examine the effects of intakes below and above FA dietary requirements on the re-set of energy metabolic pathways in Wistar rat mothers early post-birth. Methods Pregnant Wistar rats (n = 12/group) were fed an AIN93G diet with 5 levels of FA: 0X, 1X (control, 2 mg FA/kg), 2.5X, 5X or 10X. Dams were fed 1X-FA during lactation up to 1-week post-weaning (PW) when maternal metabolism is thought to re-set to homeostasis and then terminated. Weekly body weight, food intake, expression of hypothalamic food-intake neurons, mRNA and protein expression of folate-related and energy metabolic genes, and glucoregulatory hormones were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was used as a surrogate index of insulin resistance. Results Below (0X) and above (5X and 10X) FA requirements during pregnancy suppressed expression of hepatic folate metabolism (methyltetrahydrofolate (MTHF) reductase, and methionine synthase; P < 0.05) genes and led to higher 5-MTHF (P < 0.005) in blood compared to control suggesting dysregulation of 1-carbon pathways. Dams fed 0X- and 5X-FA also had higher plasma insulin and HOMA-IR than controls and changes in glucose and lipid metabolism-regulating genes in muscle (Glucose transporter-4, and Peroxisome-proliferator activated receptors; P < 0.05) but not liver or adipose at 1-week PW. The diets did not affect expression of hypothalamic food intake neurons nor body weight or food intake of the dams from birth to 1-week PW. Conclusions FA below (0X) or above (5X, 10X) requirements during pregnancy induce dysregulation of 1-carbon pathways and delay re-set of energy metabolic pathways in Wistar rat dams by 4-weeks after birth, potentially programming long-term negative metabolic effects. Funding Sources This research was supported by: Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD); EP supported by NSERC Alexander Graham Bell Canada Graduate Scholarships-Doctoral Program (CGS D).

scholarly journals [6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 48
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Rebecca Simonian ◽  
Erland Arning ◽  
Paula Ashcraft ◽  
...  
Keyword(s):  
Gene Expression ◽  
Folic Acid ◽  
Food Intake ◽  
Rna Sequencing ◽  
Control Diet ◽  
Wistar Rat ◽  
Metabolic Phenotype ◽  
Maternal Metabolism ◽  
Plasma Hormones ◽  
Plasma Leptin

[6S]-5-methyltetrahydrofolic acid (MTHF) is a proposed replacement for folic acid (FA) in diets and prenatal supplements. This study compared the effects of these two forms on maternal metabolism and hypothalamic gene expression. Pregnant Wistar rats received an AIN-93G diet with recommended FA (1X, 2 mg/kg, control), 5X-FA or equimolar levels of MTHF. During lactation they received the control diet and then a high fat diet for 19-weeks post-weaning. Body weight, adiposity, food intake, energy expenditure, plasma hormones, folate, and 1-carbon metabolites were measured. RNA-sequencing of the hypothalamus was conducted at parturition. Weight-loss from weaning to 1-week post-weaning was less in dams fed either form of the 5X vs. 1X folate diets, but final weight-gain was higher in 5X-MTHF vs. 5X-FA dams. Both doses of the MTHF diets led to 8% higher food intake and associated with lower plasma leptin at parturition, but higher leptin at 19-weeks and insulin resistance at 1-week post-weaning. RNA-sequencing revealed 279 differentially expressed genes in the hypothalamus in 5X-MTHF vs. 5X-FA dams. These findings indicate that MTHF and FA differ in their programing effects on maternal phenotype, and a potential adverse role of either form when given at the higher doses.

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 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Inhibitors Still Improve Metabolic Phenotype in Male 11β-HSD1 Knockout Mice Suggesting Off-Target Mechanisms

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4580-4593 ◽  
Author(s):  
Erika Harno ◽  
Elizabeth C. Cottrell ◽  
Alice Yu ◽  
Joanne DeSchoolmeester ◽  
Pablo Morentin Gutierrez ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Knockout Mice ◽  
Hydroxysteroid Dehydrogenase ◽  
Metabolic Parameters ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Positive Effects ◽  
Compound C

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a target for novel type 2 diabetes and obesity therapies based on the premise that lowering of tissue glucocorticoids will have positive effects on body weight, glycemic control, and insulin sensitivity. An 11β-HSD1 inhibitor (compound C) inhibited liver 11β-HSD1 by &gt;90% but led to only small improvements in metabolic parameters in high-fat diet (HFD)–fed male C57BL/6J mice. A 4-fold higher concentration produced similar enzyme inhibition but, in addition, reduced body weight (17%), food intake (28%), and glucose (22%). We hypothesized that at the higher doses compound C might be accessing the brain. However, when we developed male brain-specific 11β-HSD1 knockout mice and fed them the HFD, they had body weight and fat pad mass and glucose and insulin responses similar to those of HFD-fed Nestin-Cre controls. We then found that administration of compound C to male global 11β-HSD1 knockout mice elicited improvements in metabolic parameters, suggesting “off-target” mechanisms. Based on the patent literature, we synthesized another 11β-HSD1 inhibitor (MK-0916) from a different chemical series and showed that it too had similar off-target body weight and food intake effects at high doses. In summary, a significant component of the beneficial metabolic effects of these 11β-HSD1 inhibitors occurs via 11β-HSD1–independent pathways, and only limited efficacy is achievable from selective 11β-HSD1 inhibition. These data challenge the concept that inhibition of 11β-HSD1 is likely to produce a “step-change” treatment for diabetes and/or obesity.

scholarly journals Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo

2018 ◽  
Vol 32 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Jacob S Ballon ◽  
Utpal B Pajvani ◽  
Laurel ES Mayer ◽  
Zachary Freyberg ◽  
Robin Freyberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
Healthy Volunteers ◽  
Second Generation ◽  
Metabolic Effects ◽  
Insulin Metabolism

Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions. We hypothesized that antipsychotics induce weight gain primarily through increased caloric intake, which causes secondary dyslipidemia and insulin resistance. Subjects were phenotyped pre- and post-treatment for body weight, adiposity by dual energy X-ray absorptiometry, energy expenditure by indirect calorimetry, food intake, oral glucose tolerance, plasma lipids, glucose, insulin, and other hormones. We found significantly increased food intake and body weight but no change in energy expenditure in olanzapine-treated subjects, with associated trends towards lipid abnormalities and insulin resistance the extent of which were presumably limited by the duration of treatment. Iloperidone treatment led to modest non-significant and placebo no weightgain, lipid increases and alterations in insulin metabolism. We conclude that second generation antipsychotic drugs, as represented by olanzapine, produce their weight and metabolic effects, predominantly, by increasing food intake which leads to weight gain that in turn induces metabolic consequences, but also through other direct effects on lipid and glucose metabolism independant of food intake and weight gain.

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 High Choline During Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat Post-Weaning Diet

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1313-1313
Author(s):  
Rola Hammoud ◽  
Emanuela Pannia ◽  
Ruslan Kubant ◽  
Rebecca Simonian ◽  
G Harvey Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Wistar Rat ◽  
Visceral Adiposity ◽  
Metabolic Phenotype ◽  
Energy Regulation ◽  
High Fat ◽  
Rat Offspring ◽  
Postnatal Environment

Abstract Objectives The prenatal period is a critical time for fetal development, programming the offspring's later-life health in response to the postnatal environment. We have shown that a high maternal choline diet programs long-term energy regulation leading to higher food intake and weight-gain in mature rat offspring fed a normal fat diet. However, the offspring's response to an obesogenic post-weaning diet has not been described. We aim to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on male Wistar rat offspring's long-term metabolic phenotype. Methods Pregnant Wistar rats were fed an AIN-93G diet with either recommended choline (RC, 1g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (10%) fat (RC-NF and HC-NF) or a high (45%) fat (RC-HF and HC-HF) diet for 17 weeks. Dependent measures were body weight, food intake, visceral adiposity, plasma glucoregulatory hormones and triglycerides, and plasma and hepatic free fatty acids (FFAs). Data were analyzed with 2-way ANOVA for main effects of GD and PWD and their interaction. Measures with significant interaction effects were followed by a Student's T-test comparing groups stratified by PWD. Results HC-HF offspring had lower body weight (7%, P &lt; 0.05), and visceral adiposity (15%, P &lt; 0.05), but no difference in food intake compared to RC-HF. HC-HF offspring had lower insulin (18%, P &lt; 0.05), HOMA-IR (24%, P &lt; 0.01), and plasma triglycerides (30%, P &lt; 0.05) but no difference in leptin. Total hepatic ω-3 FFAs (30%, P &lt; 0.05) were higher and ω-6/ω-3 (P &lt; 0.01) was lower in HC-HF compared to RC-HF, indicating an ameliorated metabolic phenotype in HC-HF offspring. In contrast, HC-NF offspring had higher food intake (8%, P &lt; 0.01) and body weight (6%, P &lt; 0.05) and no difference in adiposity compared to RC-NF. They also had higher plasma leptin adjusted for adiposity (22%, P &lt; 0.05) but not insulin or HOMA-IR compared to RC-NF. Hepatic C16:1n-7/C16:0 ratio was higher in HC-NF compared to RC-NF, suggestive of dysregulated lipid metabolism. Conclusions Gestational choline supplementation is associated with improved long-term metabolic regulation in male Wistar rat offspring fed a high fat post-weaning diet. Funding Sources CIHR-Institute of Nutrition, Metabolism, and Diabetes.

scholarly journals High Choline Intake during Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat But Not a Normal Fat Post-Weaning Diet

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1438
Author(s):  
Rola Hammoud ◽  
Emanuela Pannia ◽  
Ruslan Kubant ◽  
Adam Metherel ◽  
Rebecca Simonian ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Body Weight ◽  
Food Intake ◽  
Wistar Rats ◽  
Later Life ◽  
Wistar Rat ◽  
Metabolic Phenotype ◽  
Rat Offspring ◽  
The Metabolic Syndrome

Maternal choline intakes are below recommendations, potentially impairing the child’s later-life metabolic health. This study aims to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on metabolic phenotype of male Wistar rats. Pregnant Wistar rats were fed a standard rodent diet (AIN-93G) with either recommended choline (RC, 1 g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (16%) fat (NF) or a high (45%) fat (HF) diet for 17 weeks. Body weight, visceral adiposity, food intake, energy expenditure, plasma hormones, triglycerides, and hepatic fatty acids were measured. HC-HF offspring had 7% lower body weight but not food intake, and lower adiposity, plasma triglycerides, and insulin resistance compared to RC-HF. They also had increased hepatic n-3 fatty acids and a reduced n-6/n-3 and C 18:1 n-9/C18:0 ratios. In contrast, HC-NF offspring had 6–8% higher cumulative food intake and body weight, as well as increased leptin and elevated hepatic C16:1 n-7/C16:0 ratio compared to RC-NF. Therefore, gestational choline supplementation associated with improved long-term regulation of several biomarkers of the metabolic syndrome in male Wistar rat offspring fed a HF, but not a NF, PWD.

scholarly journals High Intakes of [6S]-5-Methyltetrahydrofolic Acid Compared with Folic Acid during Pregnancy Programs Central and Peripheral Mechanisms Favouring Increased Food Intake and Body Weight of Mature Female Offspring

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1477
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Jong Yup Sa ◽  
Rebecca Simonian ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Food Intake ◽  
Leptin Receptor ◽  
Liver Weight ◽  
Female Offspring ◽  
Mature Female ◽  
Cytokine Signaling ◽  
Light Cycle ◽  
Energy Regulation

Supplementation with [6S]-5-methyltetrahydrofolic acid (MTHF) is recommended as an alternative to folic acid (FA) in prenatal supplements. This study compared equimolar gestational FA and MTHF diets on energy regulation of female offspring. Wistar rats were fed an AIN-93G diet with recommended (2 mg/kg diet) or 5-fold (5X) intakes of MTHF or FA. At weaning, female offspring were fed a 45% fat diet until 19 weeks. The 5X-MTHF offspring had higher body weight (>15%), food intake (8%), light-cycle energy expenditure, and lower activity compared to 5X-FA offspring (p < 0.05). Both the 5X offspring had higher plasma levels of the anorectic hormone leptin at birth (60%) and at 19 weeks (40%), and lower liver weight and total liver lipids compared to the 1X offspring (p < 0.05). Hypothalamic mRNA expression of leptin receptor (ObRb) was lower, and of suppressor of cytokine signaling-3 (Socs3) was higher in the 5X-MTHF offspring (p < 0.05), suggesting central leptin dysregulation. In contrast, the 5X-FA offspring had higher expression of genes encoding for dopamine and GABA- neurotransmitter receptors (p < 0.01), consistent with their phenotype and reduced food intake. When fed folate diets at the requirement level, no differences were found due to form in the offspring. We conclude that MTHF compared to FA consumed at high levels in the gestational diets program central and peripheral mechanisms to favour increased weight gain in the offspring. These pre-clinical findings caution against high gestational intakes of folates of either form and encourage clinical trials examining their long-term health effects when consumed during pregnancy.

Secretin as a satiation whisperer with the potential to turn into an obesity-curbing knight

Endocrinology ◽  
2021 ◽  
Author(s):  
Katharina Schnabl ◽  
Yongguo Li ◽  
Mueez U-Din ◽  
Martin Klingenspor
Keyword(s):  
Bariatric Surgery ◽  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Weight Control ◽  
Therapeutic Potential ◽  
Physiological Mechanism ◽  
Gut Hormones ◽  
Metabolic Effects ◽  
Beneficial Effects

Abstract The obesity pandemic requires effective preventative and therapeutic intervention strategies. Successful and sustained obesity treatment is currently limited to bariatric surgery. Modulating the release of gut hormones is considered promising to mimic bariatric surgery with its beneficial effects on food intake, body weight and blood glucose levels. The gut peptide secretin was the first molecule to be termed a hormone; nevertheless, it only recently has been established as a legitimate anorexigenic peptide. In contrast to gut hormones that crosstalk with the brain either directly or by afferent neuronal projections, secretin mediates meal-associated brown fat thermogenesis to induce meal termination, thereby qualifying this physiological mechanism as an attractive, peripheral target for the treatment of obesity. In this perspective, it is of pivotal interest to deepen our yet superficial knowledge on the physiological roles of secretin as well as meal-associated thermogenesis in energy balance and body weight regulation. Of note, the emerging differences between meal-associated thermogenesis and cold-induced thermogenesis must be taken into account. In fact, there is no correlation between these two entities. In addition, the investigation of potential effects of secretin in hedonic-driven food intake, bariatric surgery as well as chronic treatment using suitable application strategies to overcome pharmacokinetic limitations will provide further insight into its potential to influence energy balance. The aim of this article is to review the facts on secretin’s metabolic effects, address prevailing gaps in our knowledge, and provide an overview on the opportunities and challenges of the therapeutic potential of secretin in body weight control.

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.

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