Food Intake In Rats Research Articles

Olfactory Bulbectomy Model of Depression Lowers Responding for Food in Male and Female Rats: The Modulating Role of Caloric Restriction and Response Requirement.

Depression is a psychiatric disorder characterized by a marked decrease in reward sensitivity. By using the olfactory bulbectomy (OBX) model of depression, it was shown that OBX rats display enhanced drug-taking and seeking behaviors in a self-administration paradigm than sham-operated (SHAM) controls, and sex is an important regulating factor. To reveal potential strain effects, we compared the operant behavior of male and female Sprague-Dawley and Wistar OBX and SHAM rats trained to self-administer palatable food pellets. Results showed that Sprague-Dawley OBX rats of both sexes exhibited lower operant responding rates and food intake than SHAM controls. Food restriction increased responding in both OBX and SHAM groups. Female rats responded more than males, but the OBX lesion abolished this effect. In Wistar rats, bulbectomy lowered food self-administration only during the last training days. Food self-administration was not significantly affected in Wistar rats by sex. In summary, this study showed that bulbectomy significantly reduces operant responding and food intake in male and female Sprague-Dawley rats while inducing a mild reducing effect only in the Wistar strain. Strain-dependent effects were also observed in the modulating role of sex and food restriction on operant responding and palatable food intake.

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis

BackgroundMulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)—based quantitative proteomics analysis of skeletal muscle.MethodsThe anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking.ResultsAfter 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE’s ingredients.ConclusionsThis study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE.Graphical

Effects of high dietary chicken protein on obesity development of rats fed high-fat diets

This study explored the effects of dietary chicken protein at high (HCK, 40 % E) or normal (CK, 20 % E) levels on obesity development of rats fed high-fat diets. Compared with the CK diet, the HCK diet reduced body weight gain (by 15 %), epididymal adipose tissue mass (by 18.4 %), and adipocyte size (by 18.8 %) significantly without affecting the food intake of rats. It also reduced blood insulin and glycosylated serum protein (GSP) significantly by 45.4 % and 14.3 %, respectively; however, the OGTT and HOMA-IR results were not different. The HCK diet downregulated EAT transcriptomics related to the biosynthesis of cholesterol, triglycerides, and fatty acids, which were highly correlated with the most downregulated hub genes, Insig1, Srebf2, Hmgcs1, and Fasn. Therefore, high dietary chicken protein content reduced body fat accumulation, blood insulin, and GSP, and downregulated EAT transcriptomics related to lipid biosynthesis in rats fed high-fat diets.

Xiao-Ban-Xia decoction mitigates cisplatin-induced emesis via restoring PINK1/Parkin mediated mitophagy deficiency in a rat pica model

Ethnopharmacological relevanceAs a traditional Chinese anti-emetic formula, Xiao-Ban-Xia decoction (XBXD) was recorded in Golden Chamber, and has promising anti-emetic effect on chemotherapy-induced nausea and vomiting (CINV). Aim of the studyThis study aimed to determine whether the underlying mechanism of XBXD against CINV is correlated to the restoration of cisplatin-induced PINK1/Parkin mediated mitophagy deficiency and mitigation of gastrointestinal inflammation. Materials and methodsThe rat pica model was established by intraperitoneal injection of cisplatin 6 mg/kg. The daily kaolin consumption, food intake and body weight were recorded every 24 h. The pathological damage of gastric antrum and ileum were observed by hematoxylin-eosin staining. The levels of serum reactive oxygen species (ROS), interleukin-1β (IL-1β) and interleukin-1β (IL-18) were detected by ELISA. The expression of microtubule-associated protein 1 light chain 3 (LC3) in gastric antrum and ileum was detected by Immunofluorescence staining. The levels of LC3II, P62/SQSTM1, PTEN-induced putative protein kinases (PINK1), E3 ubiquitin ligase (Parkin), AMP-dependent protein kinases (AMPK), phosphorylated AMPK (p-AMPK), nuclear factor erythroid 2-related factor (Nrf2) and kelch like ECH Associated Protein 1 (Keap1) in gastric antrum and ileum were assayed by western blotting. ResultsAt 24 h and 72 h following cisplatin challenge, XBXD inhibited cisplatin-induced elevation of kaolin consumption, and improved the daily food intake and body weight loss in rats. Cisplatin-induced gastrointestinal histopathological damages were alleviated, and serum levels of ROS, IL-1β and IL-18 increases were mitigated following XBXD treatments. In gastric antrum and ileum, XBXD activated AMPK-Nrf2 signaling pathway and restored cisplatin-induced PINK1/Parkin mediated mitophagy deficiency. ConclusionsXBXD significantly ameliorated CINV in a cisplatin-induced rat pica model. The underlying anti-emetic mechanism of XBXD might be related to the activation of AMPK-Nrf2 signaling pathway and the restoration of cisplatin-induced PINK1/Parkin-mediated mitophagy deficiency in the gastrointestinal tract.

211-OR: Dual Amylin and Calcitonin Receptor Agonists Increase Mitochondrial Respiratory Capacity in Adipose Tissues of Obese Rat

Dual amylin and calcitonin receptor agonists (DACRAs) are potential therapeutic candidates for treatment of obesity. Preclinical studies have shown favorable effects of DACRAs on appetite regulation contributing to a reduction in body weight. Interestingly, the DACRA-induced effects on weight loss are superior to the effects of a suppressed food intake, suggesting an effect on energy expenditure potentially by targeting the mitochondria. We investigated the effects of long-term treatment with a class of DACRAs, namely KBPs, on body weight, food intake and mitochondrial respiratory capacity (MRC) in Sprague-Dawley rats fed a high-fat diet and treated s.c. with KBPs for 8 weeks. Moreover, a pair-fed (PF) group was used to examine food intake-independent effects of KBPs on MRC. At study end, MRC was analyzed in perirenal (pAT) and inguinal (iAT) adipose tissue using high resolution respirometry. Expectedly, KBP treatment significantly reduced body weight compared to PF and vehicle. PF was successfully KBP-matched in terms of accumulated food intake and the food intake was significantly lower than that of vehicle-treated rats. Coupled and uncoupled MRC supported by complex I+II substrates and fatty acids were significantly greater in iAT and pAT after KBP treatment indicating effects on both carbohydrate and lipid metabolism. Additionally, an increased oligomycin-induced leak-respiration was found to be independent of food intake in iAT. Further analysis will shed light on whether these changes in MRC are a result of an increased mitochondrial content or of the respiratory capacity of each mitochondrion. In conclusion, treatment with KBPs in obese rats is associated with an increased MRC in pAT and iAT and elicits effects additional to those obtained by diet-induced weight loss. This highlights DACRAs’ potential as anti-obesity agents with possible benefits on energy expenditure as a contributing cause to the DACRA-induced weight loss. Disclosure E.A.Petersen: Employee; Nordic Bioscience A/S. I.Blom: None. S.A.Melander: None. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. S.Larsen: None. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. A.T.Larsen: Employee; Nordic Bioscience A/S. Funding Innovation Fund Denmark

Aging Changes the Efficacy of Central Urocortin 2 to Induce Weight Loss in Rats.

Middle-aged obesity and aging cachexia present healthcare challenges. Central responsiveness to body-weight-reducing mediators, e.g., to leptin, changes during aging in a way, which may promote middle-aged obesity and aging cachexia. Leptin is connected to urocortin 2 (Ucn2), an anorexigenic and hypermetabolic member of the corticotropin family. We aimed to study the role of Ucn2 in middle-aged obesity and aging cachexia. The food intake, body weight and hypermetabolic responses (oxygen consumption, core temperature) of male Wistar rats (3, 6, 12 and 18 months) were tested following intracerebroventricular injections of Ucn2. Following one central injection, Ucn2-induced anorexia lasted for 9 days in the 3-month, 14 days in the 6-month and 2 days in the 18-month group. Middle-aged 12-month rats failed to show anorexia or weight loss. Weight loss was transient (4 days) in the 3-month, 14 days in the 6-month and slight but long-lasting in the 18-month rats. Ucn2-induced hypermetabolism and hyperthermia increased with aging. The age-dependent changes in the mRNA expression of Ucn2 detected by RNAscope in the paraventricular nucleus correlated with the anorexigenic responsiveness. Our results show that age-dependent changes in Ucn2 may contribute to middle-aged obesity and aging cachexia. Ucn2 shows potential in the prevention of middle-aged obesity.

AEROBIC EXERCISE PERFORMED IN ADULT LIFE MAINTAINS BODY WEIGHT AND FOOD INTAKE OF MALE RATS EVEN AFTER TRAINING INTERRUPTION

Excess weight in adult life is an important risk factor for the development ofnoncommunicable diseases. On the other hand, aerobic physical exercise programs have beenshown to be important components both in the prevention and control of these conditions.This work aims to evaluate the effects of moderate intensity training on the body weight(BW) and food intake (FI) of adult male rats. Wistar rats were obtained at 30 days old.Throughout the experimental period, they were kept in appropriate cages (4 rats per box)containing food and water, temperature (22ºC) and photoperiod (07:00 to 19:00) controlled.At PN 40 they were divided into sedentary (S) and exercised (E) groups. The BW and FI weremeasured twice a week, from 40 to 140 days old. Exercised rats performed a moderate-intensity treadmill running from PN 90 to 120. During this period, they were submitted to aneffort test to evaluate performance and control the training load (55% to 65% VO 2max ). Theresults showed that both BW and FI were not altered with the training performed during adultlife, even after 20 days of exercise cessation. More studies are needed in order to assesswhether moderate-intensity training is able to attenuates the deleterious effects observed inthe biometric and metabolic markers of adult rats programmed for obesity and/or metabolicsyndrome.

New discoveries on the interaction between testosterone and oxytocin in male rats ― Testosterone-mediated effects of oxytocin in the prevention of obesity

Sex steroid hormones are important for the maintenance of metabolism in both sexes. Oxytocin (OT) is a neuropeptide that is synthesized in hypothalamic regions, secreted from the posterior lobe of the pituitary gland, and is involved in the control of appetite, body weight, and metabolism. Estrogen and OT both play a role in the metabolism of nutrients, and OT has potential in the prevention of obesity. However, the relationship between testosterone and OT remains unclear. Therefore, the present study investigated the relationship between testosterone and OT in hypogonadal male rats and male rats receiving testosterone replacement therapy. The results obtained showed that testosterone increased serum OT levels and promoted the secretion of adiponectin from visceral fat, and reduced body fat directly and/or indirectly through OT and adiponectin. Testosterone also increased the expression of OT receptors in the hypothalamus to increase sensitivity to OT, and perhaps because of this, OT administration had the effect of reducing food intake and body weight gain in both normal and castrated rats, and this effect was stronger in normal rats. In other words, the preventative effects of OT on obesity may be synergistic with testosterone. Collectively, the present results indicate that testosterone exerts indirect effects to prevent obesity and atherosclerosis through OT and adiponectin. In conclusion, testosterone replacement therapy is useful for preventing obesity caused by hypogonadism, and OT has potential in supportive medicine to prevent obesity and adult diseases.

Subchronic toxicity study of ferric oxide nanoparticles through intragastric administration: A 94-d, repeated dose study in Sprague Dawley rats

In this study, the toxicity of ferric oxide nanoparticles (Fe2O3 NPs) administered through gavage to Sprague Dawley (SD) rats for 94 d, consecutively and the recovery after Fe2O3 NPs withdrawal for 30 d were evaluated. The vehicle control group, low-, medium-, and high-dose groups were administered with the vehicle (0.5% sodium carboxymethyl cellulose [CMC-Na]), 125, 250, and 500 mg/kg of Fe2O3 NPs, respectively, administered every morning for 94 d. There was no significant difference in the body weight, food intake, hematological, blood biochemical, and urine indices of SD rats in each administration group and the control group (P > 0.05). There was no significant difference in organ weight, organ indices, and the coefficient of the visceral brain between the SD rats in the different dosage groups and the SD rats in the vehicle control group (P > 0.05). Histopathological observations showed that there was no correlation between the pathological lesions of the organs observed in this study and the dose of Fe2O3 NPs (P > 0.05). The no-observed-adverse-effect level (NOAEL) dose of Fe2O3 NPs was initially determined to be 500 mg/kg administered to SD rats through oral gavage for 94 d, consecutively, followed by recovery after Fe2O3 NPs withdrawal for 30 d.

Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach?

Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno-colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α- and β-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and β-diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero-tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment.

Rats Treated with Somatotropin Select Diets Higher in Protein

It was previously shown that somatotropin (STH) increases growth rate, improves food efficiency and stimulates protein accretion. In rats, STH also increases food intake. This study examined the effect of exogenous STH on rats' selection of diets varying in protein content. It was hypothesized that the increase in food intake in response to STH is driven by an increased protein requirement. Rats were allowed to select between two diets varying in casein (5 and 30%) or given a diet of a single casein level (20%). In each diet group, rats were treated with 0 or 4 mg of porcine STH/d. Rats treated with STH showed greater food intake (20%) and protein accretion (125%), regardless of diet. However, the greater food intake in rats allowed to select was due to greater consumption of the high protein diet. Diet selecting, STH-treated rats consumed 75% more of the 30% casein diet than did the saline-treated controls, while consuming a similar amount of 5% casein diet. Total protein intake (g/d) was 22 and 53% greater in rats injected with STH consuming the 20% casein diet and selection diets, respectively. The results indicate that rats injected with somatotropin select a diet greater in protein when compared with those not receiving somatotropin. It is suggested that the STH-induced increase in protein accretion results in a greater demand for essential amino acids. The mechanism whereby animals are able to monitor this greater need is not clear.

Effect of Yak Meat to the Daily Ration of Scalded Rats for Wound Healing.

Treatment of burn wound healing involves infection, nutrition, psychology and rehabilitation, and proper nutritional support can promote wound healing, enhance immune function and reduce the incidence of complications. This study aimed to investigate the effects of feed containing yak meat on scalded rats' body condition and wound healing. Adopting a two-factor factorial design, the growth performance, food intake, body weight, and Lee's index of rats were measured. The wound conditions of scalded rats with different feeds (basic, basic + yak meat, and basic + yellow beef) were observed at different periods, and their wounds' hematoxylin and eosin (H&E) staining states were detected. The proliferating cell nuclear antigen (PCNA)-positive cells and apoptosis were analyzed to evaluate the effects of feed on the wound healing of scalded rats. The feed intake was the highest in the yellow beef feed group and the lowest in the yak meat feed group. The body weight was the highest in the yak meat feed group and the lowest in the yellow beef feed group. Furthermore, 45 days after scalding, the obesity index in the yak beef feed group was the closest to that of the rats before scalding. The wound recovery of the rats in the yak meat feed group was the best at 30 days, and the H&E staining results also proved that the recovery effect of the scalded rats in the yak meat feed group was better than other two groups. According to the results of PCNA and apoptosis, the yak meat feed group had lower positive cell rate and faster wound healing. The rats in the yak meat feed group recovered better than those in the other groups, and the yak beef feed had the best effect on the wound healing of the scalded rats.

Dual PTP1B/TC-PTP Inhibitors: Biological Evaluation of 3-(Hydroxymethyl)cinnoline-4(1H)-Ones

Dual inhibitors of protein phosphotyrosine phosphatase 1B (PTP1B)/T-cell protein phosphotyrosine phosphatase (TC-PTP) based on the 3-(hydroxymethyl)-4-oxo-1,4-dihydrocinnoline scaffold have been identified. Their dual affinity to both enzymes has been thoroughly corroborated by in silico modeling experiments. The compounds have been profiled in vivo for their effects on body weight and food intake in obese rats. Likewise, the effects of the compounds on glucose tolerance, insulin resistance, as well as insulin and leptin levels, have been evaluated. In addition, the effects on PTP1B, TC-PTP, and Src homology region 2 domain-containing phosphatase-1 (SHP1), as well as the insulin and leptin receptors gene expressions, have been assessed. In obese male Wistar rats, a five-day administration of all studied compounds led to a decrease in body weight and food intake, improved glucose tolerance, attenuated hyperinsulinemia, hyperleptinemia and insulin resistance, and also compensatory increased expression of the PTP1B and TC-PTP genes in the liver. The highest activity was demonstrated by 6-Chloro-3-(hydroxymethyl)cinnolin-4(1H)-one (compound 3) and 6-Bromo-3-(hydroxymethyl)cinnolin-4(1H)-one (compound 4) with mixed PTP1B/TC-PTP inhibitory activity. Taken together, these data shed light on the pharmacological implications of PTP1B/TC-PTP dual inhibition, and on the promise of using mixed PTP1B/TC-PTP inhibitors to correct metabolic disorders.

Elevated Neuropeptide Y in the Arcuate Nucleus of Young Obese Zucker Rats May Contribute to the Development of Their Overeating

Neuropeptide Y (NPY) mediates feeding behavior through a local hypothalamic network formed by the arcuate and paraventricular nuclei (the AP axis). In the hypothalamus, NPY is mainly synthesized in neurons of the arcuate nucleus. These neurons project to the paraventricular nucleus, the site where NPY has the strongest stimulatory effects on food intake of Sprague-Dawley rats. In the adult Zucker fatty rat (a genetic model of obesity with a well-established hyperphagia), NPY concentrations in these nuclei are higher than in its lean counterpart. We measured hypothalamic NPY before the appearance of altered eating behavior, e.g., in very young (16-d-old) lean and obese Zucker pups, and in pups at an age when overeating had begun, e.g., a few days after weaning at 30 d. At 30 d, NPY concentrations were significantly higher in obese than in lean rats in the arcuate nucleus (14.2 +/- 0.7 vs. 11.6 +/- 0.5 pmol/mg protein, P < 0.01). This difference was not observed at 16 d. A 160% increase was noted in the paraventricular nuclei of obese rats between 16 and 30 d of life compared with a 100% increase in the lean rats (P < 0.001). Neuropeptide Y concentration was greater in 30-d-old rats than in 16-d-old rats in other areas involved in the regulation of feeding behavior, such as the dorsomedian nuclei and lateral hypothalamus, but the values did not differ between genotypes. Higher NPY concentration was therefore detected early in young obese rats in the main hypothalamic site of NPY synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Physical Properties of Konjac Glucomannan on Appetite Response of Rats

Dietary fiber has been widely used in designing foods with a high satiating capacity, as the use of satiety-enhancing food is considered to be a promising strategy for combating obesity and the overweight condition. In the present study, partially degraded konjac glucomannan (DKGM) diets with different water-holding capacities, swelling capacities, and viscosities were used to feed rats to investigate the effects of the fiber's physical properties in regulating the appetite response of the animals. The results showed that the mass and water content of the gastrointestinal chyme increased as the diet's physical properties were enhanced by the DKGM, which increased the stomach distention of the rats and promoted satiation. Besides, the hydrated DKGM elevated the chyme's viscosity, and the retention time of the digesta in the small intestine was prolonged significantly, which resulted in an increased concentration of cholecystokinin-8, glucagon-like peptide 1, and peptide tyrosine-tyrosine in the plasma, thus helping to maintain the satiety of rats. Furthermore, the results of the behavioral satiety sequence and meal pattern analysis showed that DKGM in the diets is more likely to reduce the food intake of rats by enhancing satiety rather than satiation, and will finally inhibit excessive weight gain. In conclusion, the physical properties of dietary fiber are highly related to the appetite response, which is a powerful tool in designing food with a high satiating capacity.

The D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decrease operant responding for nicotine and food and locomotor activity in male and female rats.

The reinforcing properties of nicotine play a critical role in smoking and vaping. There is a need for treatments that decrease the reinforcing properties of nicotine and thereby improve smoking and vaping rates. Dopamine plays a role in the reinforcing properties of nicotine, but little is known about the role of dopamine D2-like receptors in nicotine intake and whether there are sex differences in the effects of dopaminergic drugs on nicotine intake. The goal of the present studies was to investigate the effects of the D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 on nicotine self-administration in male and female rats. The effects of flupentixol and L-741626 on operant responding for nicotine and food and locomotor activity in a small open field were investigated. There were no sex differences in baseline nicotine intake. The D1/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decreased operant responding for nicotine. Blockade of D1/D2-like receptors and blockade of D2-like receptors also decreased operant responding for food and decreased locomotor activity. Flupentixol induced a greater decrease in operant responding for food in males than females. However, in the other tests, there were no sex differences in the effects of the dopamine receptor antagonists. Blockade of D1/D2-like receptors with flupentixol and D2-like receptors with L-741626 decreases nicotine and food intake in rats of both sexes. These compounds also decrease locomotor activity which might be indicative of a sedative effect.

Effect of edible bird's nest and N-acetylneuraminic acid on gut microbiota in different stages of pregnant rats fed with zinc deficient diet

Zinc deficiency diet during pregnancy and lactation have become an important hidden danger to the healthy development of offspring. Therefore, natural supplements are urgently needed to treat gut microbiota disorder induced by zinc deficiency diet. The study aims to investigate the effects of edible bird's nest (EBN) and N-acetylneuraminic acid (NANA) on gut microbiota in different stages of pregnant rats fed with zinc deficient diet. Zinc deficiency diet was used to induce gut microbiota disorder in pregnant rats. High-throughput 16S rRNA gene sequencing and bioinformatics analysis technology were also conducted. And the relationship between body weight, food intake and organ index of pregnant rats and differential microbiota was analyzed. It was found that dietary zinc deficiency can lead to gut microbiota disturbance in pregnant rats, which can be improved by EBN and NANA to increase beneficial bacteria such as Bacteroides, Bifidobacterium and Lactobacillus, and reduce the harmful ones such as Enterococcus, Turicibacter and Parabacteroides. These results can not only deepen the understanding of the effects of EBN and NANA on gut microbiota in pregnant rats, but also lay an important foundation for the further utilization of them in the pregnant population.

Initial Pharmacological Characterization of a Major Hydroxy Metabolite of PF-5190457: Inverse Agonist Activity of PF-6870961 at the Ghrelin Receptor.

Preclinical and clinical studies have identified the ghrelin receptor [growth hormone secretagogue receptor (GHSR)1a] as a potential target for treating alcohol use disorder. A recent phase 1a clinical trial of a GHSR1a antagonist/inverse agonist, PF-5190457, in individuals with heavy alcohol drinking identified a previously undetected major hydroxy metabolite of PF-5190457, namely PF-6870961. Here, we further characterized PF-6870961 by screening for off-target interactions in a high-throughput screen and determined its in vitro pharmacodynamic profile at GHSR1a through binding and concentration-response assays. Moreover, we determined whether the metabolite demonstrated an in vivo effect by assessing effects on food intake in male and female rats. We found that PF-6870961 had no off-target interactions and demonstrated both binding affinity and inverse agonist activity at GHSR1a. In comparison with its parent compound, PF-5190457, the metabolite PF-6870961 had lower binding affinity and potency at inhibiting GHSR1a-induced inositol phosphate accumulation. However, PF-6870961 had increased inhibitory potency at GHSR1a-induced β-arrestin recruitment relative to its parent compound. Intraperitoneal injection of PF-6870961 suppressed food intake under conditions of both food restriction and with ad libitum access to food in male and female rats, demonstrating in vivo activity. The effects of PF-6870961 on food intake were abolished in male and female rats knockout for GHSR, thus demonstrating that its effects on food intake are in fact mediated by the GHSR receptor. Our findings indicate that the newly discovered major hydroxy metabolite of PF-5190457 may contribute to the overall activity of PF-5190457 by demonstrating inhibitory activity at GHSR1a. SIGNIFICANCE STATEMENT: Antagonists or inverse agonists of the growth hormone secretagogue receptor (GHSR)1a have demonstrated substantial potential as therapeutics for alcohol use disorder. We here expand understanding of the pharmacology of one such GHSR1a inverse agonist, PF-5190457, by studying the safety and pharmacodynamics of its major hydroxy metabolite, PF-6870961. Our data demonstrate biased inverse agonism of PF-6870961 at GHSR1a and provide new structure-activity relationship insight into GHSR1a inverse agonism.

POTENSI EKSTRAK ETANOL BIJI JINTEN HITAM (NIGELLA SATIVA L.) MENURUNKAN KADAR GLUKOSA DARAH PADA TIKUS PUTIH (Rattus norvegicus) JANTAN KONDISI HIPERGLIKEMIK.

Diabetes mellitus is a disease characterized by elevated blood sugar levels, one of which is often exposed to free radicals. The purpose of this study was to determine the effects of hypoglycemia and ethanol extract on black cumin seeds. This may affect the reduction in blood glucose levels and the increase in weight gain and food intake induced by alloxan in laboratory rats.&#x0D; This study is an experimental laboratory study using only a post-test class design. Subjects of this study were his 30 male Wistar rats who were adjusted for his type 2 diabetes using alloxan induction. The rats he divided into six groups. group II negative control alloxan 150 mg/kg body weight; group III positive control glibenclamide 0.45 mg/kg body weight; kg body weight, Group V black cumin seed ethanol extract dosage 200 mg/kg body weight.&#x0D; The results showed that black seed ethanol extract at doses of 100, 200, and 400 mg/kg body weight reduced blood glucose levels and increased body weight and food intake in experimental rats. The most effective dose is 400 mg/kg body weight.

Oral Administration of Artemisia argyi Polysaccharide Increases Estrogen Level and Maintains Blood Lipid Homeostasis in Ovariectomized Rats

Introduction: Artemisia argyi polysaccharide (AAP) has a beneficial effect on menstruation-related symptoms and the potential regulation of lipid metabolism. It is expected to be a safe and effective ingredient for estrogen deficiency and lipid metabolic disorders. Here, we investigate the effect of AAP on body weight gain, estrogen level, and blood lipid changes in ovariectomized (OVX) rats. Methods: Thirty-six female Wistar rats were randomly divided into six treatment groups, including a sham-operated (Sham) group, OVX group, estrogen replacement (OVX + E2) group, and AAP treatment (OVX + 125, 250, 500 mg/kg AAP) group. The body weight and feed intake were recorded every week. The level of estrogen and blood lipid was determined. The gene expressions and protein expressions of estrogen receptors (ERs), fatty acid synthetase (FAS), acetyl CoA carboxylase 2 (ACC2), and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) were determined. Results: AAP treatment significantly decreased the body weight gain and average daily food intake of rats in the OVX group. Treatment with AAP significantly increased the relative weight of the uterus, plasma estrogen level, and the gene expression and protein expression of ER-α in the uterus. For blood lipids, plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced by AAP treatment in OVX rats. AAP treatment decreased the expression of FAS and HMGR in the liver of OVX rats. Furthermore, AAP treatment significantly increased the gene expression of ACC2, the protein expression of P-ACC2, and the ratio of P-ACC2/ACC2. Conclusion: In summary, AAP treatment exerts beneficial effects on body weight gain and lipid metabolism disorder induced by ovariectomy through increasing estrogen levels, inhibiting FAS, and promoting fatty acid oxidation.