Stimulated Weight Gain Research Articles

Soda intake influences phenotype, antioxidants and inflammatory status in high protein-fed wistar rats

An increasing population of people, especially young adults who exercise, consume high protein diets along with carbonated drinks. While there are numerous studies on the effect of high protein diets, there is a need to understand how protein diets in combination with carbonated drinks impact physiology. In order to assess these effects on wistar rats’ phenotype, antioxidants and inflammatory profiles, 64 wistar rats were divided into dietary groups of 8 male and 8 female animals each. The animals were fed standard diet as control (chow), chow and carbonated soda, a high protein diet (48.1% energy from protein) and a high protein diet with carbonated soda according to their groups.Body measurements, blood glucose levels, serum insulin levels, lipid peroxidation, antioxidant activity, adipokines and inflammatory markers concentrations were all determined. At the end of the study, body measurements, inflammatory markers and adipokine concentration were increased in animals fed the high protein diet and high protein-soda diet. There was a decrease in antioxidant and lipid peroxidation levels in protein fed male and female animals but those fed protein in combination with soda had increased lipid peroxidation levels.In conclusion, high protein diet in combination with carbonated soda impacts physiology differently from a high protein diet alone, and may stimulate weight gain, oxidative stress and HPD-related inflammation in Wistar rats.

Rest phase snacking increases energy resorption and weight gain in male mice

ObjectiveSnacking, i.e., the intake of small amounts of palatable food items, is a common behavior in modern societies, promoting overeating and obesity. Shifting food intake into the daily rest phase disrupts circadian rhythms and is also known to stimulate weight gain. We therefore hypothesized that chronic snacking in the inactive phase may promote body weight gain and that this effect is based on disruption of circadian clocks. MethodsMale mice were fed a daily chocolate snack either during their rest or their active phase and body weight development and metabolic parameters were investigated. Snacking experiments were repeated in constant darkness and in clock-deficient mutant mice to examine the role of external and internal time cues in mediating the metabolic effects of snacking. ResultsChronic snacking in the rest phase increased body weight gain and disrupted metabolic circadian rhythms in energy expenditure, body temperature, and locomotor activity. Additionally, these rest phase snacking mice assimilated more energy during the inactive phase. Body weight remained increased in rest phase snacking wildtype mice in constant darkness as well as in clock-deficient mutant mice under a regular light–dark cycle compared to mice snacking in the active phase. Weight gain effects were abolished in clock-deficient mice in constant darkness. ConclusionsOur data suggest that mistimed snacking increases energy resorption and promotes body weight gain. This effect requires a functional circadian clock at least under constant darkness conditions.

Sleep loss in male rats contributes more to weight gain during sleep disruption than stress assessed by corticosterone

Sleep disruption (SD) promotes stress which may mediate the effect of SD induced by noise on bodyweight gain and food intake. We determined if the change in bodyweight during SD caused by noise was driven by stress (assessed by corticosterone) and whether the effects of noise on SD, stress and bodyweight were specific to the method of SD or a consequence of SD per se. We isolated stress from SD due to noise by exposing rats to noise during the darkphase to test whether darkphase noise stimulated weight gain, stress and food intake. Male Sprague-Dawley rats slept undisturbed, were exposed to noise during both circadian phases (lightphase vs darkphase) and lightphase gentle handling. Bodyweight, food intake, physical activity, vigilance states, and plasma corticosterone were determined. Darkphase noise did not affect vigilance states. Unlike lightphase noise, darkphase noise and lightphase gentle handling did not stimulate weight gain or food intake. Only gentle handling significantly increased corticosterone levels. Noise during the lightphase increasesed weight gain and food intake by causing SD and these effects were not driven by stress as assessed by corticosterone. These results may have significant implications for developing translational models of insomnia-induced obesity in humans.

ФІЗІОЛОГО-БІОХІМІЧНІ ПОКАЗНИКИ ПРОРОСТКІВ ПШЕНИЦІ М’ЯКОЇ (TRITICUM AESTIVUM L.) ПРИ МОДЕЛЮВАННІ ВОДНОГО ДЕФІЦИТУ ЗА ДІЇ МЕТАБОЛІЧНО АКТИВНИХ СПОЛУК

The article presents a comparative description of the effect of metabolically active substances and their compositions on individual physiological and biochemical parameters of soft wheat in drought conditions. The study involved the use of 7 options for seed treatment: control (untreated seeds + distilled water); vitamin E solution (10-8M) - E; ubiquinone-10 solution (10-8M) - Q; methionine solution (0.001%) - M; paraoxybenzoic acid solution (PОBA) (0.001%) - P; MgSO4 solution (0.001%) - Mg; compositions of substances: vitamin E (10-8M) + ubiquinone-10 (10-8M) - EQ; vitamin E (10-8M) + methionine (0.001%) + POBA (0.001%) - EMР; vitamin E (10-8M) + methionine (0.001%) + POBA (0.001%) + MgSO4 (0.001%) - EMРMg. The experimental water deficiency was simulated by a 12% solution of PEG 6000.
 It was found that the germination of soft wheat seeds under the action of metabolically active substances in a solution of osmotically active substance PEG 6000 did not lead to a decrease in the germination energy of the experimental seeds compared to the control. Determination of germination of soft wheat seeds showed that treatment with Mg solution and compositions of EQ, EMР, EMРMg reduced the inhibitory effect of PEG 6000, showed a stimulating effect and increased seed germination. The highest seed germination in water-deficient conditions was found by treatment with EMРMg composition.
 Studies of the effect of metabolically active substances on the processes of rhizogenesis of soft wheat seedlings have shown that seeds’ treatment with the solution of methionine most effectively stimulated the formation of roots on wheat seedlings in conditions of water deficiency. Ubiquinone-10 solution stimulated linear root growth in conditions of water deficiency most effectively, exceeding the control by 16,9%, neutralizing the inhibitory effect of PEG 6000. High efficiency in stimulating linear root growth of wheat seedlings in drought conditions was observed after using the compositions EMР and EMPMg, and solutions of ubiquinone-10 and MgSO4. Ubiquinone-10 solution and composition EQ showed the best stimulating effect on the development of a shoot of soft wheat under water deficiency. Seeds treated with solutions of ubiquinone-10, MgSO4 and EQ had the highest rates of weight gain of roots. The seeds treated with ubiquinone-10 solution stimulated weight gain of the shoot more effectively under water deficiency (exceeded the control by 41.8%).
 Treatment of soft wheat seeds with compositions EQ and EMPMg stimulated the accumulation of free proline in wheat seedlings most effectively under water deficiency. Proline is an indicator of plant adaptation in conditions of slow water supply and increased drought resistance of soft wheat.
 Thus, seeds pre-sowing treatment with the studied metabolically active compounds and their compositions could be used as elements of technology in the cereals cultivation under water deficiency.

Do gluten peptides stimulate weight gain in humans?

Observations from animal and in vitro laboratory research, and anecdotal evidence, have led to the suggestion that gluten consumption stimulates weight gain by the presence of peptides expressing opioid activity. Another proposed mechanism is that gluten peptides decrease resting energy expenditure resulting in a positive energy balance. In order to induce such effects in vivo, intact food peptides must be absorbed in sufficient quantities, remain intact in the blood for sufficient time to have long‐lasting biological activity and bind to receptors involved in appetite, satiety and energy regulation. However, although peptides from food may pass from the intestine into the blood in extremely low quantities, they are generally rapidly degraded by plasma and vasculum‐bound aminopeptidases, resulting in very short half‐lives and loss of bioactivity. At present, gluten peptide sequences that influence regulators of energy metabolism have not been identified. Furthermore, data on the quantitative absorption of gluten peptides in the blood stream, their stability and lasting bioactivity are also lacking. Therefore, there is no evidence for proposed effects on driving appetite by the brain, nor on energy expenditure and weight gain. Furthermore, the level of overweight observed in various countries appears to be independent of the level of wheat consumption, and abundant observational evidence in humans shows that the levels of gluten consumption are neither related to daily calorie intake nor to BMI. This narrative review therefore discusses the proposed effects of gluten on bodyweight (BW) and putative biological mechanisms in the light of the current evidence.

Эффективность применения кормовой добавки «Абиопептид» в скотоводстве

This article presents materials on the production test of the Abiopeptid feed additive on calves of the Holstein breed raised in Sovkhoz Golovkovo LLC MTF Kryukovo, two groups of 20 calves were formed in each experimental group, the Abiopeptid feed additive was soldered at a rate of 1 ml/kg live masses. As a result, the use of the Abiopeptid feed additive at a dose of 1 ml / kg of calf live weight has been established that it does not negatively affect the physiological parameters of the clinical status of animals. The use of the Abiopeptid feed additive increases the average daily gain of calves by 100,0 g compared with the control group. The results of blood tests suggest a reliable stimulating effect of the Abiopeptid feed supplement on metabolic processes, increasing the parameters characterizing hematopoiesis. Thus, the Abiopeptid feed additive can be recommended for use by animals during the period of active growth and development of the body, to stimulate weight gain, and activate animal metabolism, and prevent anemia and malnutrition. In order to determine the effectiveness of the feed additive, we studied the indicators of the clinical status of calves and a biochemical and general blood test.

SAT-167 Dehydroepiandrosterone Sulfate (DHEAS) Levels Predict Weight Gain in Women with Anorexia Nervosa

Introduction: Anorexia nervosa (AN) and atypical AN (defined as weight loss and all the psychological features of AN but BMI>18.5 kg/m2) are serious disorders characterized by undernutrition and complicated by endocrine dysregulation. Predictors of recovery, including serum biomarkers, are lacking. Prior studies have suggested that higher urinary free cortisol (UFC) may predict weight gain in women with AN, but 24-hour urine collections are not feasible in a real-world setting. Like cortisol, the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfated form DHEAS, which has a longer half-life, are stimulated by ACTH. We hypothesized that DHEAS levels would correlate with UFC and be a predictor of weight gain in women with AN.Methods: We prospectively studied 34 women with AN and atypical AN, mean age 27.4 ± 7.7 years (mean ± SD), who received placebo in a randomized trial. AN and atypical AN were diagnosed by SCID. Baseline DHEAS and 24-hour UFC were measured by LC-MS/MS (Endocrine Sciences, Calabasas Hills, CA). Weight and body composition were assessed at baseline and 6 months later by DXA and cross-sectional abdominal CT at L4.Results: At baseline, mean weight was 51.3 ± 4.9 kg. Of the 18 subjects who gained weight (range 0.1–10.3 kg), 28% were eumenorrheic, 39% amenorrheic, and 33% on oral contraceptives at baseline; baseline reproductive status was similar for subjects who did not subsequently gain weight. In the group as a whole, mean baseline DHEAS level was 173 ± 70 µg/dL (0.7 ± 0.3 times the mean normal range for age) and mean baseline UFC for subjects who completed testing (n=15) was 20 ± 18 µg/24h (normal range 0–50 µg/24h). Higher DHEAS levels at baseline predicted weight gain over 6 months (r=0.61, p<0.001), which remained significant after controlling for age, baseline BMI, OCP use, and SSRI/SNRI use (p<0.001); none of these covariates were predictors of weight gain. Baseline DHEAS levels predicted an increase in fat mass (r=0.40, p=0.03) and appendicular lean mass (r=0.38, p=0.04) by DXA, and abdominal fat by CT (r=0.60, p<0.001); the associations remained significant after controlling for the above factors. UFC did not predict change in weight (r=0.37, p=0.17) or body composition. DHEAS levels were positively associated with UFC (r=0.61, p=0.02).Conclusion: In women with AN, higher DHEAS levels are a predictor of weight gain and increases in fat mass, skeletal muscle mass, and abdominal fat. Serum DHEAS correlates with UFC, a predictor of weight gain in prior studies. DHEAS may be a more practical biomarker of recovery, as 24-hour urine collections are challenging. Further studies are needed to determine whether higher DHEAS levels are a marker of global adrenal stress response and a reflection of higher cortisol levels, which may stimulate weight gain, or an independent predictor of weight gain in AN and atypical AN, perhaps through neuromodulation.

Influence of DAFS-25+polizon composition on blood and functional state of liver of steers at fattening

Summary. The disbalanced feeding and the uneven distribution of micro- and macroelements in the environment leads to a trace element, in particular hypomelanosis. To accelerate the growth and preservation of young farm animals include in the diet of various biological additives and drugs, which include selenium. For stimulation of weight gain in the livestock industry, as well as for the prevention and treatment of pathological processes in addition to micro - and macrouse amino acids, primarily methionine. The aim of this work was to study the influence of composition of DAFS-25+Polizon on morpho-biochemical parameters of blood and functional state of the liver in fattening bulls of black-motley breed in the conditions of the Republic of Bashkortostan. Experiments using were conducted on bull-calves of black-motley breed of the properties in the properties age from 6 to 15 months. The first experimental group during the experiment was additionally given the composition of DAFS-25+Polizon at a dose of 2 mg/kg, the animals of the control group received a standard diet. To assess the impact of the composition DAFS-25+Polizon on metabolism cattle studied morphological and biochemical indicators of blood and conducted histological examination of the liver. It is established that the use of the composition of DAFS-25+Polizon at a dose of 2 mg/kg increases the number of erythrocytes and hemoglobin in the experimental group and reduces the amount of white blood cells. The serum content of total protein, phosphorus and calcium increases in the group of experimental animals. Microscopic examination of the liver revealed no changes in the structure of the organ and hepatocytes in the experimental group, whereas in the control group hemodynamic disorders and dystrophic changes in liver cells were observed. Thus, the use of the composition DAFS-25+Polizon at a dose of 2 mg/kg of live weight in fattening bulls black-and-white breed contributes to the increase of redox processes in the body, stimulation of metabolism, prevent the development of liver disorders of cellular mechanisms of metabolism, optimizes the structure of the liver, which generally provides higher productivity.

ВЛИЯНИЕ КОРМОВОЙ ДОБАВКИ НА ОСНОВЕ БЕЛКОВОГО ГИДРОЛИЗАТА НА КЛИНИЧЕСКИЙ СТАТУС ТЕЛЯТ

This article presents materials on the production test of feed additive based on the protein hydrolyzate Abiotoniс on calves of the Holstein breed raised in «Sovkhoz Golovkovo» in dairy farm «Kryukovo». Two groups of XNUMX calves were formed in each experimental group, the Abiotonic feed additive was soldered at a rate of XNUMX ml/kg live weight. In order to determine the effectiveness of the feed additive, we studied the indicators of the clinical status of calves and a biochemical and general blood test. As a result, the use of the Abiotonic feed additive at a dose of XNUMX ml/kg of calf live weight has been established that it does not negatively affect the physiological parameters of the clinical status of animals. The use of the abiotonic feed additive increases the average daily gain of calves by XNUMX gramms compared with the control group. The results of blood tests suggest a reliable stimulating effect of the Abiotonic feed supplement on metabolic processes, increasing the parameters characterizing hematopoiesis. Thus, the Abiotonic feed additive can be recommended for use by animals during the period of active growth and development of the body, to stimulate weight gain, and activate animal metabolism, and prevent anemia and hypotrophy.

Refeeding syndrome as treatment complication of anorexia nervosa.

Refeeding syndrome (RS) is one of the serious complications during treatment of anorexia nervosa. It includes hormonal and metabolic changes that occur during the process of refeeding in chronically malnourished patient when nutrition is introduced in an excessive and improper amount. RS manifests in water-electrolyte imbalances, including hypophosphatemia (the mostimportant diagnosticmarker), hypokalemia, hyponatremia, hypomagnesaemia, fluid retention, vitamin deficiency and metabolic acidosis. It applies to either oral and parenteral supplementation. In the treatment of malnourished patients with anorexia nervosa, it is essential to establish an initial caloric amount that will stimulate weight gain from the beginning of treatment, increase its effectiveness while minimizing the risk of RS. Recent research suggests that the current recommendations may be too stringent in this respect and require further updating. Awareness of the risks associated with RS, including significant mortality, appears to be currently insufficient also among physicians. There is a need for far more specialized multidisciplinary centers for patients with anorexia nervosa and also appropriate algorithms and standards of care for that population. The aim of this paper is to systematize the current knowledge about RS and RS prevention, to increase awareness of its occurrence and present the results of the latest research on safe resupplementation of patients suffering from anorexia nervosa.

THE EFFECTIVENESS OF CANNABINOIDS FOR THE TREATMENT OF CACHEXIA IN HIV-POSITIVE PATIENTS

Knowledge of the role of the endocannabinoid system in the modulation of immune functions, the influence of mood, the regulation of appetite, gives us the right to think about the possibility of use of cannabinoids for the treatment of cachexia. Cachexia, also known as weight loss syndrome, is a common problem in patients with human immunodeficiency virus (HIV). Weight loss syndrome is defined as a loss of at least 10% of the body weight. In HIV-positive patients, weight loss syndrome has been associated with chronic diarrhea, fatigue, and fever for at least 30 days. This serious situation leads to significant morbidity and mortality for these patients. The use of cannabinoids to improve appetite and regain weight in HIV-positive patients is recommended, but it is unclear whether they are truly safe and effective. MARINOL (dronabinol), 2.5, 5 or 10 mg tablets is the only synthetic cannabinoid (tetrahydrocannabinol (THC) isomer) intended for oral administration and FDA approved for two indications: treatment of anorexia associated with weight loss in people with acquired immune deficiency syndrome (or HIV-positive patients) and vomiting caused by chemotherapy in people whose nausea and vomiting have not improved with usual antiemetics. In the United States, Marinol is treated as a non narcotic drug with a very low risk of physical and mental dependence (categorized into level III of controlled substances). The dosage for treatment of weight loss depends on tolerability, from 1 x 2.5 mg /day to 2 x 10 mg /day. The medicine is stated to be taken before meals: before dinner when is administered once daily or before breakfast and dinner if the total dose is divided into twice daily intake. An online literature review published by June 2018 identified a total of six randomized clinical trials (RCTs) that were conducted to evaluate the effects of dronabinol for the treatment of cachexia in HIV-positive patients. They included a total of 298 patients. In 5 of the six studies conducted, the effects of dronabinol were compared with placebo, and in only one study the effects of dronabinol were compared with megestrol acetate. Only one of the six studies was classic placebo-controlled study that reported the effects of dronabinol on body weight correction, while in other studies the effects of dronabinol on body weight correction were secondary notification. This study is also the only study on which base indication for dronabinol are approved. Studies show that dronabinol at doses of 5mg /day stimulates weight gain compared with placebo. Dronabinol compared to megestrol showed a lack of effect. The conclusion of these studies, however, is that use of cannabinoids can have a positive effect on improving appetite and weight gain in HIV-positive patients.

Anti-nutritional effect of phytates – extraphosphoric effect of phytase

The increase of animal and poultry production can be achieved by the effective use of fodder, including vegetable feed. However, it is known that the vegetable feed can contain anti-nutrients (phytic acid or its salts). They reduce the nutrient availability in the diet. That is why, the research aim is the description of the phytate influence on the body and the definition of the right feed phytases for fodder production. Phosphorus is responsible for the energy supply to the body for metabolic processes. It plays a significant role in the metabolism of proteins, fats and carbohydrates. It takes part in the synthesis of enzymes, hormones, vitamins. Phosphorus ensures the stability of the skeleton of animals along with calcium. However, the predominant part of phosphorus is not available for animals in the vegetable feed as it is presented by phytates, which do not split in the gastrointestinal tract (GIT) of animals. When phytates get into the acidic environment of the stomach they ionize and react with positively charged minerals, proteins, amino acids creating compounds that are inaccessible for further digestion. The availability of phosphorus from phytates is provided by the phytase adding to the fodder, which not only splits phytates, but also reduces their anti-nutritional effect by concentration decreasing. From the present-day data it is known that phytates contain difficult soluble phosphorus. They also make it difficult to absorb another biologically active nutrients from fodder. The enrichment of the animal diet with microbial phytase makes calcium, zinc and copper be more accessible. It improves digestibility of food and stimulates weight gain. Phytase activity determined by the laboratory method does not allow to make up a conclusion about its expected effectiveness for animals. At present it is almost impossible to conduct such complex research and to use the dynamic modeling of digestion processes in the laboratory. The decision about the appropriate use of proposed preparations with phytase in the fodder is made on the basis of the production test. Keywords: animal feed, enzymes, phytase, anti-nutritional effect of phytates, extra phosphoric effect of phytase, activity of the feed preparations of phytase.

Growth Components of Cow's Milk: Emphasis on Effects in Undernourished Children.

Cow's milk is a core ingredient in foods for prevention and treatment of undernutrition in children. It promotes growth, but there is limited knowledge of which components in milk have growth-stimulating effects. To discuss the growth-stimulating effects of milk in undernourished children with emphasis on protein, lactose, and minerals. We reviewed literature on dairy and growth in undernourished children. Cow's milk has a specific stimulating effect on linear growth, even in well-nourished children, and it may stimulate weight gain and muscle accretion in wasted children. Dairy protein has high protein quality scores with no major differences between whey protein concentrate and dried skimmed milk. Lactose has potential growth-stimulating effects, and the high content of potassium, phosphorus, magnesium, and zinc in milk is also likely to stimulate growth. Furthermore, a high dairy content reduces the amount of antinutrients from plant protein. Dairy protein, lactose, and bioavailable minerals all have potential growth-stimulating effects, which make cow's milk an important ingredient in foods for undernourished children. Different dairy ingredients vary with regard to protein amount and quality, content of lactose, and minerals, and thereby growth stimulating effects. This should be taken into consideration when deciding which dairy ingredient to use. Challenges include the relatively high cost of dairy. Therefore, future studies should include cost-effectiveness analysis and assessment of the desirable content of each growth-promoting milk component.

Partial Sleep Deprivation Reduces the Efficacy of Orexin-A to Stimulate Physical Activity and Energy Expenditure.

Sufficient sleep is required for weight maintenance. Sleep deprivation due to noise exposure stimulates weight gain by increasing hyperphagia and reducing energy expenditure (EE). Yet the mechanistic basis underlying the weight gain response is unclear. Orexin-A promotes arousal and negative energy balance, and orexin terminals project to the ventrolateral preoptic area (VLPO), which is involved in sleep-to-wake transitions. To determine whether sleep deprivation reduces orexin function in VLPO and to test the hypothesis that sleep deprivation would attenuate the orexin-A-stimulated increase in arousal, physical activity (PA), and EE. Electroencephalogram, electromyogram, distance traveled, and EE were determined in male Sprague-Dawley rats following orexin-A injections into VLPO both before and after acute (12-h) and chronic (8 h/d, 9 d) sleep deprivation by noise exposure. Orexin-A in the VLPO significantly increased arousal, PA, total EE, and PA-related EE and reduced sleep and respiratory quotient before sleep deprivation. In contrast to after acute sleep deprivation in which orexin-A failed to stimulate EE during PA only, orexin-A failed to significantly increase arousal, PA, fat oxidation, total EE, and PA-related EE after chronic sleep deprivation. Sleep deprivation may reduce sensitivity to endogenous stimuli that enhance EE due to PA and thus stimulate weight gain.

Use of ghrelin in cachexia syndrome: a systematic review of clinical trials.

Ghrelin is a hormone that stimulates weight gain and increases appetite. For these reasons, it has been used for treatment of cachexia syndrome. The aim of this systematic review was to examine the use of ghrelin in cachexia patients to better understand the most prevalent clinical outcomes, particularly since the type and dosage of hormone used and the route and duration of administration often varies. A search of electronic databases (MEDLINE, SciELO, Embase, Cochrane Library, and Clinical Trials.gov) was limited to original articles describing interventions in adult humans, with no limits for publication date or language. Articles were searched independently by 2 reviewers, from October 2013 to April 2015. Studies were eligible for inclusion if they were conducted in adult patients with a diagnosis of cachexia and provided information on type of ghrelin or analogue used, route of administration and dose administered, duration of intervention, outcomes, and clinical trial study design. Data were extracted independently by 2 reviewers using a preconstructed spreadsheet. Initially, 573 references were identified. Seven articles describing 379 participants were selected for review. Ghrelin was found to have a predominantly positive effect on growth hormone plasma levels, weight gain, increases in lean mass, and reductions in loss of adipose tissue. Although the studies reviewed here report positive results, there is still little evidence available on the use of ghrelin to treat cachexia. Further research is required to determine conclusively whether the use of ghrelin in patients with cachexia is a viable therapy.

Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11β-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11β-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11β-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

Early human handling in non-weaned piglets: Effects on behaviour and body weight

Early handling of animals including tactile stimulation (TS) has been shown to have beneficial effects on the physical and psychological development of species where considerable maternal interaction, e.g. in the form of licking, already occurs. But little is known about the magnitude of these effects, if any, in species without this natural mechanism. Piglets from 13 litters (N=127) were subjected to four treatments: AH – all piglets in a litter received TS; NH – none of the piglets in a litter received TS; 50/50H – half of a litter received TS and 50/50NH – half of a litter did not receive TS. The TS was performed by a human stroking the back of the piglet for 2min from 5 to 35 days of age. At 4 weeks of age the piglets were tested twice in an open-field/human-approach test, with either a familiar (F) or an unfamiliar person (U). Body weight was measured at birth, 5, 9 and 12 weeks of age. In the tests, AH and 50/50H piglets allowed more physical contact, regardless of the familiarity of the person (AH: 22.5±2.3 F; 24.1±2.3 U, 50/50H: 18.1±2.2 F; 25.3±2.2 U, P=0.05). Additionally, AH piglets vocalized least and were least often in the perimeter zone (PZ) of the arena (AH grunts: 6.0±0.8, P=0.002; 12.8±0.8, P=0.0005; 18.1±0.8, P=0.08; AH PZ: 3.9±0.8, P=0.009; 9.1±0.8, P=0.003; 12.6±0.7, P=0.004 in isolation, stationary and moving person phase, respectively). In contrast, NH piglets vocalized most and were most often in the PZ. 50/50NH had higher body weights at 12 weeks than 50/50H, whereas AH and NH piglets were intermediate (AH: 36.9±0.9, NH: 35.6±1.0, 50/50H: 34.2±1.3, 50/50NH: 37.8±1.3, P=0.03). This study suggests that early handling changed the way piglets reacted to challenging situations in that handled piglets showed behaviour suggesting they were less fearful in a novel environment and less fearful of being handled by people in general. Interestingly though, the early handling did not result in the same beneficial effects on the physical development of the piglets, as handled piglets were not heavier. Instead, it was the 50/50NH piglets that were the heaviest, implying that the daily presence of a human moving around in the pen to handle the 50/50H piglets seemed to stimulate weight gain.

New prospects in the treatment of diabetes mellitus

Cardiovascular complications, a major cause for disability and morbidity in diabetes mellitus (DM), constitute the greatest threat of the diabetes epidemic. Glycemic stability within the therapeutic targets is a prerequisite to prevention of micro- and macrovascular complications of DM. Traditional therapies are aimed at cardinal defects determining development of type 2 diabetes mellitus (T2DM). Unfortunately even in combination they fail to deliver long-term glycemic control without stimulation of weight gain and increase in hypoglycemic risks with negative cardial, renal and hepatic impact. Preservation of beta-cell secretion capacity is also hardly attainable. Incretin-based therapy is a novel, actively developed approach that influences gut hormone physiology for better glycemic control. So far research efforts have yielded two classes of drugs: GLP-1 mimetics and DPP-4 inhibitors. Both are regarded nowadays for a number of important benefits, including beta-cell function improvement, adjusted to human physiology (i.e. stimulation of insulin secretion ?as needed? by the body, - hence low hypoglycemic risk). They also feature positive cardiovascular and body weight effects, thereby taking an important position in complex DM treatment.

The metabolic effects of Olanzapine and Topiramate in rats and humans

In humans the anti-psychotic Olanzapine (OLZ) has negative side effects on metabolism: it causes weight gain and increases the risk of developing type 2 Diabetes. The anti-convulsant Topiramate (TPM) has the opposite effects: it reduces body weight and improves insulin sensitivity. Because of this, it has been proposed to use TPM to counteract OLZs side effects. The underlying mechanisms by which OLZ and TPM influence metabolism are unknown. To study this, we performed a series of studies in both rats and humans. In rats we administered OLZ and TPM via a permanent intragastric cannula, to mimic oral drug administration, and found that chronic OLZ treatment stimulates weight gain and causes insulin resistance reflected by increased insulin responses during an intravenous-glucose tolerance test OLZ also decreased locomotor activity and core temperature, pointing to a reduction in energy expenditure. OLZ also increased weight gain in humans, accompanied with decreased daily physical activity, reduced body temperature and increased baseline and glucosestimulated insulin levels during an oral glucose tolerance test. TPM reduced the OLZ-induced overeating and weight gain in both rats and humans combined with an increased postprandial satiety rating (in humans). We conclude that, in both rats and humans, a reduction in energy expenditure may explain, at least in part, the OLZ effects on weight gain and that the OLZ-induced effects on insulin resistance has a peripheral side of action. We also conclude that TPM may prevent the negative metabolic side effects induced by OLZ. Supported by: Top Institute Pharma.

P03-224 - Schizophrenia- a Syndrome of Insulin Impairment

IntroductionSchizophrenia is a human specific disease, unknown in other primates. Low adiposity during childhood was associated with a greater risk of developing schizophrenia, but this disease has a higher incidence in the obese children and adults, too.ObjectivesWe developed a new hypothesis on the human evolution. According to it, changes in the activity of the IGF1 (insulin-like growth factor1)/insulin pathway (altered in human pathological conditions such as the psychiatric disorders) could be responsible for the appearance of certain specific human traits.AimsThis hypothesis predicts that schizophrenia should result from a deviation of the normal IGF1/insulin signaling in brain in both directions. A drug that increases insulin resistance should improve the condition in the slim patients and worsen them in the obese patients.MethodsA multi-center double-blind study on palmitate paliperidone (pp), the major active metabolite of the antipsychotic risperidone (that increases insulin resistance and stimulates weight gain), was conducted. 25–150 mg eq pp was injected intramuscular (into the deltoid muscle or the gluteal muscle) at 1 week interval for 1 year in a double blind study in patients with acute symptoms.ResultsOur preliminary observations based on the Positive and Negative Syndrome Scale (PANSS) total scores showed that the slim patients had statistically the best response to pp and the worse effects were observed in the obese patients. The study is still ongoing.ConclusionsThese results suggest that schizophrenia is a polarized disease with 2 major phenotypes- one with either insulin sensitivity or obesity and insulin resistance.