Chow Pellets Research Articles

Conditioned overconsumption is dependent on reinforcer type in lean, but not obese, mice.

Associative learning can drive many different types of behaviors, including food consumption. Previous studies have shown that cues paired with food delivery while mice are hungry will lead to increased consumption in the presence of those cues at later times. We previously showed that overconsumption can be driven in male mice by contextual cues, using chow pellets. Here we extended our findings by examining other parameters that may influence the outcome of context-conditioned overconsumption training. We found that the task worked equally well in males and females, and that palatable substances such as high-fat diet and Ensure chocolate milkshake supported learning and induced overconsumption. Surprisingly, mice did not overconsume when sucrose was used as the reinforcer during training, suggesting that nutritional content is a critical factor. Interestingly, we also observed that diet-induced obese mice did not learn the task. Overall, we find that context-conditioned overconsumption can be studied in lean male and female mice, and with multiple reinforcer types.

Phytochemical investigation and experimental evaluation of Panchavalkala for Lekhana Karma w.s.r. to Antihyperlipedemic Activity

Panchavalkala the barks of five trees i.e., Nyagrodha (Ficus benghalensis L.), Udumbara (Ficus racemosa L.), Ashwatha (Ficus religiosa L.), Plaksha (Ficus virens Aiton) and Parisha (Thespesia populnea (L.)Sol.ex Correa) are also known as Pancha Ksheeri Vrikshas in use since Vedic period. The plant samples were collected in Sharad Rutu (late autumn) from their natural habitat, extracted using ethanol and water and subjected for the phytochemical analysis. The study was aimed to evaluate Antihyperlipidemic effect (Lekhana Karma) of Panchavalkala Bark extracts individually and in combination (1:1:1:1:1) both in ethanolic and aqueous extracts on serum lipid profile in Cafeteria died (HFD) induced hyperlipidemia in SD rats. The animals were divided into fifteen groups of six animals each. The normal control group continued to be fed laboratory pellet chow ad libitum. The cafeteria diet-control group received the cafeteria diet in addition to the normal pellet diet (NPD). The remaining 13 groups were fed with the cafeteria diet and NPD along with standard control Atorvastatin 10mg/kg and the test drug p.o for 30 days. Treatment with the test substance PVK AE and PVK EE at doses of 200mg/kg body weight p.o. controlled and regulated the HFD induced weight gain, glucose and lipids in the blood when compared against high fat diet control (P< 0.05). PVK bark extracts are capable of exhibiting significant antihyperlipidemic activity in HFD induced SD rats. Taken together, this study strongly suggests that PVK bark extracts might be an efficient way for treatment of hyperlipidemia.

The Role of Chlorella vulgaris in Attenuating Infertility Induced by Cadmium Chloride via Suppressing Oxidative Stress and Modulating Spermatogenesis and Steroidogenesis in Male Rats.

Cadmium (Cd) is an environmental pollutant known as endocrine disruptor . Cd has been reported to induce perturbations of the testicular functions and the subsequent decline of the male fertility of both animals and humans. Chlorella vulgaris (ChV) a species of green microalga has been reported to have multiple beneficial activities such as anti-inflammatory, antioxidant, and antiapoptotic effects. Thus, this work was conducted to declare the benefits of Chlorella vulgaris (ChV) (500 mg/kg doses) against cadmium chloride CdCl2 (2 mg/kg doses) toxicity on the main and accessory reproductive organs' weight, structure, and function of male rats. Briefly, 40 adult male rats in 4 groups (n = 10) were used as follows; control, ChV, CdCl2, and CdCl2+ChV. (i) The 1st group was kept as control fed on pellet chow and water ad libitum. (ii) The second group is Chlorella vulgaris (ChV) group fed with C. vulgaris alga for 10 days (500 mg/kg BW). (iii) The third group was administrated CdCl2 (2mg/kg BW) via subcutaneous injection (S/C) daily for 10 days. (iv) The fourth group administered both CdCl2 and ChV with the abovementioned doses daily for successive 10 days. Our observations declared that cadmium exhibited an adverse influence on the testes and prostate gland architecture indicated by seminiferous tubule destruction, testicular edema, degeneration of Leydig cells, and prostate acini damage. All together affect the epididymal semen quality and quantity including sperm viability, motility, and count. Interestingly, ChV could restore the testicular architecture and spermatozoa regeneration accompanied by semen quality improvement and increased reproductive hormones including testosterone. On the other side, ChV suppresses reactive oxygen species (ROS) formation via enhancement the antioxidant-related genes in the testicular tissue including SOD, CAT, GSH, and MDA and maintaining spermatocyte survival via suppression of apoptotic related genes including caspase3 and activating steroidogenic related genes including StAR and HSD17β3 in the cadmium-treated testes. In this study, ChV could enhance male fertility under normal or stressful conditions and ameliorate the adverse effects of hazardous heavy metals that are widely distributed in our environment.

Perampanel’s forgiveness factor in a variable medication adherence paradigm in a rat model of chronic epilepsy

BackgroundPoor medication adherence contributes to increased morbidity and mortality in patients with epilepsy and may be under-addressed in clinical practice. Ethical concerns make it impossible to study the impact of medication nonadherence in clinical trials, but our previous work emphasizes the importance of using preclinical approaches to address these questions. With over 30 clinically available antiseizure medicines (ASM’s), it remains an important question to understand the relationship between poor adherence and seizure incidence across mechanistically distinct ASM’s, including the broad-spectrum ASM, perampanel (PER).MethodsWe formulated PER into chow pellets to deliver to rats in a 100% fully adherent or 50% variable nonadherent paradigm via our novel automated medication-in-food delivery system. Chronic oral dosing was initiated in male rats with chronic epilepsy while monitoring 24/7 for videoEEG evidence of seizures during a 4-week placebo baseline and 4-week treatment phase. PER concentrations were monitored in plasma at 1-week intervals and correlated with degree of seizure control. The relationship between missed doses and extended patterns of nonadherence were correlated with breakthrough seizures.ResultsFully adherent rats demonstrated a median reduction in seizure frequency of 50%, whereas nonadherent rats had a median increase of 54%. Plasma concentrations of PER were stable over the 4-week treatment period in both fully adherent and nonadherent groups, with levels being twice as high in fully adherent animals. There was no correlation between a single missed dose or series of missed doses and the incidence of breakthrough seizures. However, those animals in the nonadherent group that received PER for every meal during a 24-h period had a reduced likelihood of seizure incidence.ConclusionsIf our preclinical data is supported in the clinic, PER’s favorable pharmacokinetic profile in humans, combined with a lowered risk of breakthrough seizures suggests that it may provide a certain forgiveness factor if a dose is missed within a 24-h window.

Substitutability of nicotine and sucrose in rats: A behavioral economic analysis

Despite considerable evidence suggesting that sweet foods are a substitute for nicotine in humans, no formal behavioral economic analysis of this interrelationship has been conducted in nonhumans. The purpose of the present study was to examine this phenomenon in rats using concurrent schedules of sucrose pellet, chow pellet, and nicotine reinforcer delivery. Rats responded on separate levers that delivered sucrose pellets, chow pellets, or nicotine infusions under concurrent fixed-ratio (FR) 1 schedules for each commodity within a closed economy. Following stable food and nicotine intake, the unit price of either sucrose or nicotine (the primary commodity) was increased while the two alternative commodities remained unchanged. Substitution was quantified using a behavioral economic cross-price model, as well as a novel commodity relation index that normalizes consumption of dissimilar commodities. Asymmetrical partial substitution was observed, wherein sucrose served as a partial substitute for nicotine, but nicotine failed to substitute for sucrose. Moreover, sucrose was a stronger partial substitute for nicotine than chow in most rats. These findings indicate that substitution of food for nicotine depends on the type of food. These findings mirror the selective increase in carbohydrate intake that can occur during smoking cessation and demonstrate a behavioral economic mechanism that may mediate it.

Effect of long-term intake of liquid nutrition on the development and maintenance of the weight and size of the skull, mandible, and teeth in rats.

The consistency of the diet may affect the development and maintenance of the muscular and bony parts of the masticatory apparatus. Therefore, we investigated the effect of chronic intake of liquid nutrition (Fresubin) on the growth and maintenance of the weight and size of the skull, mandible, and teeth in Wistar rats fed with liquid nutrition during different developmental periods: (i) from weaning to adulthood, (ii) only in the juvenile period, or (iii) only in adulthood. We found that in all groups of rats fed with liquid nutrition, the skull and the mandible were significantly lighter in weight than those of control rats fed exclusively with pelleted chow from weaning to adulthood. In addition, in rats fed with liquid nutrition, the length of the mandible was significantly increased, whereas the height of the mandible and the length of the upper incisors were reduced. Our data indicate that food consistency may profoundly affect the growth pattern and the maintenance of the mass and size of skull bones and teeth during different periods of life. The extent of the effect was found to depend on the period during which liquid nutrition is provided and on the duration of its intake. In conclusion, the findings indicate that prolonged intake of liquid nutrition can significantly affect the development of the bone part of the masticatory apparatus.

Inositol hexaphosphate promotes intestinal adaptation in short bowel syndrome via an HDAC3-mediated epigenetic pathway.

Short bowel syndrome (SBS) has high morbidity and mortality rates, and promoting intestinal adaptation of the residual intestine is a critical treatment. Dietary inositol hexaphosphate (IP6) plays an important role in maintaining intestinal homeostasis, but its effect on SBS remains unclear. This study aimed at investigating the effect of IP6 on SBS and clarified its underlying mechanism. Forty male Sprague-Dawley rats (3-week-old) were randomly assigned into four groups (Sham, Sham + IP6, SBS, and SBS + IP6 groups). Rats were fed standard pelleted rat chow and underwent resection of 75% of the small intestine after 1 week of acclimation. They received 1 mL IP6 treatment (2 mg/g) or sterile water daily for 13 days by gavage. Intestinal length, levels of inositol 1,4,5-trisphosphate (IP3), histone deacetylase 3 (HDAC3) activity, and proliferation of intestinal epithelial cell-6 (IEC-6) were detected. IP6 treatment increased the length of the residual intestine in rats with SBS. Furthermore, IP6 treatment caused an increase in body weight, intestinal mucosal weight, and IEC proliferation, and a decrease in intestinal permeability. IP6 treatment led to higher levels of IP3 in feces and serum, and higher HDAC3 activity of the intestine. Interestingly, HDAC3 activity was positively correlated with the levels of IP3 in feces (r = 0.49, P = 0.01) and serum (r = 0.44, P = 0.03). Consistently, IP3 treatment promoted the proliferation of IEC-6 cells by increasing HDAC3 activity in vitro. IP3 regulated the Forkhead box O3 (FOXO3)/Cyclin D1 (CCND1) signaling pathway. IP6 treatment promotes intestinal adaptation in rats with SBS. IP6 is metabolized to IP3 to increase HDAC3 activity to regulate the FOXO3/CCND1 signaling pathway and may represent a potential therapeutic approach for patients with SBS.

Fasting alters p75NTR and AgRP mRNA expression in rat olfactory bulb and hippocampus

Classic non-homeostatic structures involved in food intake regulation are reciprocally influenced by metabolic signals. Orexigenic peptides expressed in the olfactory bulb (OB) and hippocampus (HP) modulate olfactory processing and memory, respectively. Hypothalamic circuits also modulate feeding behavior by activating and releasing Agouti-related peptide (AgRP) in response to orexigenic signals. An adequate response to fasting requires the expression of p75 neurotrophin receptor (p75NTR) in AgRP neurons. The present study aimed to determine whether there is a role for p75NTR and AgRP in the OB and HP on the feeding behavior of fasted rats. A group of fasted rats (FG) was confronted with a decision-making paradigm in a T-maze containing a standard chow pellet (CP), and the same pellet coated with a phenolic-rich avocado paste extract (AVO) on either end; their OB and HP were then analyzed with histological and molecular tools. FG rats had briefer feeding latencies, as compared to control rats fed ad libitum (median latencies: 55.4 vs 191.7 min, p = 0.032). They also had reduced cell counts in both brain structures, as compared to satiated rats. AgRP mRNA was not expressed in the HP of either group, however, it was found in the OB. p75NTR mRNA was expressed in both brain structures of FG rats. These results suggest that contrasting metabolic states (fasted or satiated) motivate different feeding responses, which are influenced by p75NTR and AgRP mRNA expression in non-homeostatic food intake brain structures.

Efficacy of Supplemental Diet Gels for Preventing Postoperative Weight Loss in Mice ( Mus musculus).

This study investigated whether the use of commercially available diet gels prevented the postoperative weight loss associated with major survival surgery in mice. C57BL/6 mice were divided into 3 groups ( n = 9 per group) that received moistened chow pellets alone or with one of 2 commercially available diet gels. Mice began receiving the test diets 3 d before surgery (baseline) and were weighed daily for 7 d after surgery. On day 0, mice underwent ventral midline laparotomy, during which the intestines were manipulated for 2 min and a segment of jejunum was briefly clamped. Compared with the baseline value for the same group, body weights for the mice that received moistened chow only were significantly lower on all postoperative days (days 1 through 7). In contrast, body weights of mice that received both moistened chow and diet gel differed from baseline only on days 2 and 3 for one product and were never different from baseline for the other product. This study indicates that the combination of diet gel and moistened chow prevented or mitigated postoperative weight loss after a laparotomy procedure in mice.

Effect of Nyctanthes arbor-tristis on cardiovascular parameters and metabolic syndrome in fructose-induced hypertensive rats

Objectives: We investigated the effects of methanolic extract of Nyctanthes arbor-tristis (MNAT) 100, 200 and 400 mg/kg/day post-operative for 6 weeks on ECG, basal mean arterial blood pressure (MABP), heart rate, respiratory rate, vascular reactivity, antioxidant activities of enzyme superoxide dismutase (SOD) and catalase (CAT), levels of thiobarbituric acid reactive substances (TBARS), serum levels of leptin, adiponectin, glucose, triglycerides, cholesterol, uric acid, insulin, sodium and potassium in fructose-fed rats. Materials and Methods: A high-fructose-diet (fructose 10%, w/v) ad libitum for 6 weeks was used to induce hypertension in male Wistar rats (150–200 g). Sixty albino Wistar rats were randomly divided into a group of six, each group containing 10 animals. Group I was considered as normal control which received chow pellets and normal drinking water ad libitum for 6 weeks. Group II received fructose (10%) solution instead of normal drinking water for 6 weeks. Group III received fructose (10%) solution instead of drinking water ad libitum and MNAT at a dose of 100 mg/kg post-operative for 6 weeks. Group IV received fructose (10%) solution instead of drinking water ad libitum and MNAT at a dose of 200 mg/kg post-operative for 6 weeks. Group V received fructose (10%) solution instead of drinking water ad libitum and MNAT at a dose of 400 mg/kg post-operative for 6 weeks. Group VI received fructose (10%) solution instead of drinking water ad libitum and enalapril at a dose of 10 mg/kg post-operative for 6 weeks. Physiological parameters, ECG, heart rate, respiratory rate and blood pressure vascular reactivity to various drugs were measured and recorded by the invasive method. The antioxidant activities of enzyme SOD and CAT, levels of TBARS, along with serum levels of leptin, adiponectin, glucose, triglycerides, cholesterol, uric acid, insulin, sodium and potassium were measured. Cumulative concentration-response curve (CCRC) of Ang II and acetylcholine (Ach) was recorded. Results: MNAT treatment decreased MABP and altered vascular reactivity to various catecholamines. The activities of SOD and CAT enzymes exhibited a considerable increase and the levels of TBARS in the liver were reduced by MNAT treatment. MNAT has shown decrease in the plasma level of triglycerides, cholesterol, insulin and sodium while increase in plasma adiponectin and potassium levels. The CCRC of Ang II was shifted towards the right by MNAT treatment using an isolated strip of rat ascending colon. MNAT treatment increased the contractile characteristics of the rat ascending colon in the CCRC of ACh as compared to the fructose-treated group. MNAT treatment reduced fructose-induced tissue damage due to the consequence of metabolic syndrome (MetS). MNAT is rich in flavonoids and, therefore, has powerful antioxidant properties. The findings show that by battling oxidative stress caused by fructose (10%) and reducing Ang II activity, MNAT may be able to prevent the development of high blood pressure caused by fructose. Conclusion: MNAT has antihypertensive action and reverses MetS in the fructose-induced hypertensive rat model.

Assessment of Binge-Like Eating of Unsweetened vs. Sweetened Chow Pellets in BALB/c Substrains.

Binge eating disorder (BED) is defined as chronic episodes of consuming large amounts of food in less than 2 h. Binge eating disorder poses a serious public health problem, as it increases the risk of obesity, type II diabetes, and heart disease. Binge eating is a highly heritable trait; however, its genetic basis remains largely unexplored. We employed a mouse model for binge eating that focused on identifying heritable differences between inbred substrains in acute and escalated intake of sucrose-sweetened palatable food vs. unsweetened chow pellets in a limited, intermittent access paradigm. In the present study, we examined two genetically similar substrains of BALB/c mice for escalation in food consumption, incubation of craving after a no-food training period, and compulsive-like food consumption in an aversive context. BALB/cJ and BALB/cByJ mice showed comparable levels of acute and escalated consumption of palatable food across training trials. Surprisingly, BALB/cByJ mice also showed binge-like eating of the unsweetened chow pellets similar to the escalation in palatable food intake of both substrains. Finally, we replicated the well-documented decrease in anxiety-like behavior in BALB/cByJ mice in the light-dark conflict test that likely contributed to greater palatable food intake than BALB/cJ in the light arena. To summarize, BALB/cByJ mice show binge-like eating in the presence and absence of sucrose. Possible explanations for the lack of selectivity in binge-like eating across diets (e.g., novelty preference, taste) are discussed.

Pharmacological Investigation of Anti-obesity Effect of Cyperus Rotundus

According to WHO, obesity is a not unusual place fitness ailment of lipid and carbohydrate metabolism that consequences from immoderate fats accumulation in adipose tissue, liver, skeletal muscle etc. This research was focused on the development and Investigation of Anti-Obesity effect of Cyperus Rotundus in obese rats. The plant- Nagarmotha was collected from Moradabad region and authenticated by the botanist. Firstly, the calibration curve was plotted. Animals were obtained from the animal house maintained at Faculty of Pharmacy, IFTM University, Moradabad, IN. Animals were free to access pellet chow diet and water ad libitum. They were kept as per CPCSEA Guidelines for one week and kept on fasting for 24 hours prior sacrificing the rodents. The rats were divided into 6 groups, each containing 6 animals. It includes Group 1: Normal Diet Control, Group 2: High caloric Diet control (HCD), Group 3: HCD + Orlistat (5 mg/kg), Group 4: HCD + EEN (100 mg/kg), Group 5: HCD+ EEN (200 mg/kg and Group 6: HCD + EEN (300 mg/kg). Each rat was evaluated after the continuous treatments for different parameters such as body weight & food intake, Total Body Electrical Conductivity (TOBEC), blood glucose levels, oral glucose tolerance test, histopathological studies for adipose tissue and liver, RNA Extraction and Semi-Quantitative PCR Analysis and liver and kidney functions test. In results, Ethanolic Extract of Nagarmotha (EEN) at all the three doses- 100mg/kg, 200mg/kg and 300mg/kg significantly exhibited lipid lowering effects when compared to standard group treated with Orlistat and control or high calories diet animals, in all the parameters. The effects were observed in dose-dependent manner, in ascending order with increase in dose. In conclusion, it may be said that EEN is a potential anti-lipidemic agent. This research suggests to characterize and isolate the main moiety responsible for its pharmacological activity (as anti-obesity) and confirm the mode of action- at which receptor subtype binding occurs.

A Western Diet Influences Ventilation in a Sex‐Specific Manner and Prevents Expression of Respiratory Neuroplasticity in Adult Rats

Estrogen impacts neuroplasticity in multiple areas of the central nervous system including within respiratory neural networks. Previous research from our group established that estrogen is necessary to permit expression of phrenic long‐term facilitation (pLTF), a form of respiratory neuroplasticity induced by acute, intermittent hypoxia (AIH). Many factors influence circulating estrogen levels such as age, gender, and diet. Specifically, the Western Diet is associated with increased levels of circulating estrogen in post‐menopausal women. Common to cultures of the Western Hemisphere, the Western Diet is characterized by high intakes of red and processed meats, sweets, fried foods, and refined grains with the addition of a high intakes of sugar, salt, omega 6 fatty acids, and a reduction of omega 3 fatty acids. Since the Western Diet is associated with high estrogen levels, and estrogen appears to play a critical role in expression of respiratory neuroplasticity, we assessed whether rats fed a Western Diet would have altered respiratory function and expression of AIH‐induced pLTF. Experimental rats of both sexes were fed a Western Diet in pellet form for 12 weeks and compared to rats consuming standard pellet chow. Weekly whole body plethysmography was used to measure ventilation and changes in ventilatory responses over time. At the conclusion of 12 weeks, AIH‐induced phrenic LTF was measured in anesthetized, vagotomized, and mechanically ventilated rats. Surprisingly, neither sex exhibited a change in body weight in response to the 12‐wk Western Diet, nor was baseline ventilation different between experimental groups within the same sex. However, with hypoxic challenge, male rats on the Western Diet showed lower breathing frequency and higher tidal volumes, while females on the Western Diet exhibited the opposite effects. Also, AIH‐induced pLTF was abolished in male and female Western Diet rats despite an increase in circulating estrogen levels in Western Diet Rats as measured by ELISA assay. These preliminary data suggest that the Western Diet may induce progressive changes in ventilation and loss of respiratory neuroplasticity independent of increased circulating estrogen levels.

Effect of activation of liver X receptor alpha on cardiac & hepatic ABCC10 and SLC17A5 drug transporters in hypercholesterolemic rat model

BackgroundLiver x receptor α (LXRα) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. Oxysterols (endogenous oxidized cholesterol derivatives) are the most potent endogenous LXRα-agonist. LXRα has a direct impact on several members of drug transporter superfamilies; ATP-binding cassette (ABC) and solute linked carrier (SLC). ObjectiveThe current study aimed to investigate the effect of LXRα-activation by either endogenous oxysterols or a synthetic LXRα-agonist (LXRa) such as TO901317 on hepatic and cardiac gene expression of ABCC10 and SLC17A5 drug transporters in an experimentally hypercholesterolemic rat model. Methods48 male rats were divided randomly into four groups (n = 12); control group rats received vehicle; hypercholesterolemic group (HCH group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks; (LXRa group) rats were fed standard pellet chow for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg; (HCH + LXRa group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg. ResultsOur findings revealed that hypercholesterolemia and LXRa significantly activated LXRα to varying degrees in both hepatic and cardiac tissues with subsequent alteration of LXRα and ABCC10 gene expression. Whereas, SLC17A5 gene expression was primarily affected by elevated serum cholesterol level and unmediated via LXRα-activation. ConclusionsAccordingly, it was concluded that ABCC10 is a specific LXRα-target gene and that LXRα autoregulates its own expression in rats.

Anatabine, Nornicotine, and Anabasine Reduce Weight Gain and Body Fat through Decreases in Food Intake and Increases in Physical Activity.

Obesity is a leading cause of preventable death in the United States. Currently approved pharmacotherapies for the treatment of obesity are associated with rebound weight gain, negative side effects, and the potential for abuse. There is a need for new treatments with fewer side effects. Minor tobacco alkaloids (MTAs) are potential candidates for novel obesity pharmacotherapies. These alkaloids are structurally related to nicotine, which can help reduce body weight, but without the same addictive potential. The purpose of the current study was to examine the effects of three MTAs (nornicotine, anatabine, and anabasine) and nicotine on weight gain, body composition, chow intake, and physical activity. We hypothesized that the MTAs and nicotine would reduce weight gain through reductions in chow intake and increases in physical activity. To test this, male Sprague Dawley rats were housed in metabolic phenotyping chambers. Following acclimation to these chambers and to (subcutaneous (sc)) injections of saline, animals received daily injections (sc) of nornicotine, anabasine, anatabine, or nicotine for one week. Compared to saline-injected animals that gained body weight and body fat during the treatment phase, injections of nornicotine and anatabine prevented additional weight gain, alongside reductions in body fat. Rats receiving anabasine and nicotine gained body weight at a slower rate relative to rats receiving saline injections, and body fat remained unchanged. All compounds reduced the intake of chow pellets. Nornicotine and nicotine produced consistent increases in physical activity 6 h post-injection, whereas anabasine’s and anatabine’s effects on physical activity were more transient. These results show that short-term, daily administration of nornicotine, anabasine, and anatabine has positive effects on weight loss, through reductions in body fat and food intake and increases in physical activity. Together, these findings suggest that MTAs are worthy of further investigations as anti-obesity pharmacotherapies.

Retrospective Evaluation of a Minor Dietary Change in Non-Diabetic Group-Housed Long-Tailed Macaques (Macaca fascicularis).

Simple SummaryMacaques in captivity are prone to becoming overweight and obese, which may cause several health and welfare problems. Diet likely plays an important role herein. In an attempt to reduce overweight incidence and related health problems, a minor dietary change was implemented in our long-tailed macaque breeding colony. The provisioning of bread was replaced by grains and vegetables, while the basic diet of monkey chow remained the same. Overweight status did not differ after dietary change, but some biochemical parameters related to glycemic response and lipid metabolism improved. This study emphasizes the importance of evaluating husbandry changes and shows that relatively minor dietary adjustments may improve animal health and welfare.Macaques in captivity are prone to becoming overweight and obese, which may cause several health problems. A diet that mimics the natural diet of macaques may prevent these problems and improve animal welfare. Adjusting captive diets towards a more natural composition may include increasing fiber content and lowering the glycemic index, i.e., reducing the impact on blood glucose levels. Such a dietary change was implemented in our long-tailed macaque (Macaca fascicularis) breeding colony. The basic diet of monkey chow pellets remained the same, while the supplementary provisioning of bread was replaced by grains and vegetables. This study is a retrospective evaluation, based on electronic health records, that investigated whether this minor dietary change had a beneficial effect on relative adiposity and overweight-related health parameters in 44 non-diabetic, group-housed, female long-tailed macaques. Relative adiposity was measured with a weight-for-height index and blood samples were collected during yearly health checks. Glycemic response and lipid metabolism were evaluated using several biochemical parameters. Relative adiposity and overweight status did not differ after dietary change. Yet, relatively heavy individuals generally lost body weight, while relatively lean individuals gained body weight, leading to a more balanced body weight dynamic. Dietary change did not affect HbA1c and triglyceride levels, while fructosamine and cholesterol levels were significantly reduced. Thus, the minor dietary change had no significant effect on overweight status, but some biochemical parameters related to the risk of diabetes and cardiovascular disease were positively affected. This study emphasizes the importance of evaluating husbandry changes and that critically reviewing husbandry practices can provide valuable insights to improve animal health and welfare.

Contrasting Effects of Fasting on Liver-Adipose Axis in Alcohol-Associated and Non-alcoholic Fatty Liver.

Background: Fatty liver, a major health problem worldwide, is the earliest pathological change in the progression of alcohol-associated (AFL) and non-alcoholic fatty liver disease (NAFL). Though the causes of AFL and NAFL differ, both share similar histological and some common pathophysiological characteristics. In this study, we sought to examine mechanisms responsible for lipid dynamics in liver and adipose tissue in the setting of AFL and NAFL in response to 48 h of fasting.Methods: Male rats were fed Lieber-DeCarli liquid control or alcohol-containing diet (AFL model), chow or high-fat pellet diet (NAFL model). After 6–8 weeks of feeding, half of the rats from each group were fasted for 48 h while the other half remained on their respective diets. Following sacrifice, blood, adipose, and the liver were collected for analysis.Results: Though rats fed AFL and NAFL diets both showed fatty liver, the physiological mechanisms involved in the development of each was different. Here, we show that increased hepatic de novo fatty acid synthesis, increased uptake of adipose-derived free fatty acids, and impaired triglyceride breakdown contribute to the development of AFL. In the case of NAFL, however, increased dietary fatty acid uptake is the major contributor to hepatic steatosis. Likewise, the response to starvation in the two fatty liver disease models also varied. While there was a decrease in hepatic steatosis after fasting in ethanol-fed rats, the control, chow and high-fat diet-fed rats showed higher levels of hepatic steatosis than pair-fed counterparts. This diverse response was a result of increased adipose lipolysis in all experimental groups except fasted ethanol-fed rats.Conclusion: Even though AFL and NAFL are nearly histologically indistinguishable, the physiological mechanisms that cause hepatic fat accumulation are different as are their responses to starvation.

Varying modalities of perinatal exposure to a pesticide cocktail elicit neurological adaptations in mice and zebrafish.

Epidemiological indications connect maternal and developmental presence or exposure to pesticides with an increased risk for a spectrum of neurological trajectories. To provide pre-clinical data in support of this hypothesis, we used two distinct experimental models. First, female and male mice were fed immediately prior to mating, and the resulting pregnant dams were continously fed during gestation and lactation periods using chow pellets containing a cocktail of six pesticides at tolerable daily intake levels. Male and female offspring were then tracked for behavioral and invivo electrophysiological adaptations. Second, a zebrafish model allowed us to screen toxicity and motor-behavior outcomes specifically associated with the developmental exposure to a low-to-high concentration range of the cocktail and of each individual pesticide. Here, we report anxiety-like behavior in aging male mice maternally exposed to the cocktail, as compared to age and gender matched sham animals. In parallel, invivo electrocorticography revealed a decrease in gamma (40-80Hz) and an increase of theta (6-9Hz) waves, delineating a long-term, age-dependent, neuronal slowing. Neurological changes were not accompanied by brain structural malformations. Next, by using zebrafish larvae, we showed an increase of all motor-behavioral parameters resulting from the developmental exposure to 10μg/L of pesticide cocktail, an outcome that was not associated with midbrain structural or neurovascular modifications as assessed by invivo 2-photon microscopy. When screening each pesticide, chlorpyrifos elicited modifications of swimming parameters at 0.1μg/L, while other components provoked changes from 0.5μg/L. Ziram was the single most toxic component inducing developmental malformations and mortality at 10μg/L. Although we have employed non-equivalent modalities and timing of exposure in two dissimilar experimental models, these outcomes indicate that presence of a pesticide cocktail during perinatal periods represents an element promoting behavioral and neurophysiological modifications. The study limitations and the possible pertinence of our findings to ecotoxicology and public health are critically discussed.

High fructose-enriched diet synergistically exacerbates endocrine but not metabolic changes in letrozole-induced polycystic ovarian syndrome in Wistar rats

BackgroundPolycystic Ovarian Syndrome (PCOS) is a multifactorial endocrine-metabolic disorder that highly contributes to the prevalence of infertility globally. The increased consumption of refined carbohydrate, particularly fructose has been associated with pandemic metabolic disorders, including in women of reproductive age. However, the effects of high fructose consumption (FRD) on endocrine and metabolic disorders associated with PCOS are not clear. Therefore, this study investigated the effects of FRD on endocrine/metabolic changes in letrozole-induced PCOS in Wistar rats. Materials and methodsTwenty-eight adult female Wistar rats were randomly allotted into 4 groups and treated with vehicle, letrozole (LET; 0.5 mg/kg), FRD (D-fructose chow pellet mixture) and LET + FRD. The treatment lasted for 21days. ResultsData showed a significant increase in ovarian weight, liver weight, luteinising hormone (LH), testosterone and decrease in follicle stimulating hormone as well as moderate histopathological changes in the fallopian tube, uterus and liver of animals with PCOS. FRD-treated group showed a significant increase in ovarian weight and liver weight but no significant alteration in hormonal profile or histopathological changes in uterus and fallopian tube. However, FRD significantly altered hormonal profile with consequent histopathological changes in fallopian tube and uterus but FRD did not alter ovarian/liver weight or blood glucose in animals with PCOS when compared with animals without PCOS. ConclusionThe present results demonstrate that FRD synergistically aggravates endocrine but not metabolic changes in PCOS, suggesting that FRD might deteriorate endocrine-related phenotypes in PCOS.

Evaluation of anti-obesity potential of aqueous extract of Achyranthes aspera Linn. in high fat diet induced obese rats

BackgroundObesity, reached epidemic proportions globally is often associated with life threatening comorbidities. The unavailability of safe and effective long term medications for obesity in modern pharmacotherapy forces the scientific community to explore the potential of Ayurvedic traditional healers as they are considered safe and effective.ObjectiveTo explore the anti-obesity potential of aqueous extract of aerial parts of Achyranthes aspera L. (AEAA), a traditional healer in high fat diet (HFD) induced obese rats.MethodsAEAA was prepared and subjected to in-vitro pancreatic lipase inhibition assay and in-vivo anti-obesity studies. For in-vivo studies, HFD fed obese prone Wistar albino rats were divided into five experimental groups (Group II to VI): animals fed with standard pellet chow served as normal control (Group I) while, animals continued with HFD alone served as obese control (Group II); Group III, IV and V were administered AEAA at a dose of 100, 200 and 300 mg/kg b.w. respectively along with HFD; and animals administered orlistat (30 mg/kg bw) along with HFD served as standard control (Group VI). All the drugs were administered orally once a day for a period of 60 days. At the end of the experimental period various physical, biochemical and histopathological observations were made.ResultsIn-vitro studies showed AEAA partially but not significantly inhibited the activity of pancreatic lipase. Data of in-vivo studies revealed, significant reduction in body weights, fat pad weights and organ weights upon AEAA treatment. Elevated levels of glucose, insulin, leptin, lipid profiles and antioxidant status were also brought back to normal.ConclusionThe obtained results clearly suggested that AEAA possess pronounced anti-obesity potential.