Chronic liquid nutrition intake induces obesity and considerable but reversible metabolic alterations in Wistar rats

We have previously described the development of substantial, but reversible obesity in Wistar rats fed with palatable liquid nutrition (Fresubin). In this study, we investigated changes in serum hormone levels, glycemia, fat mass, adipocyte size, and gene expression of adipokines and inflammatory markers in adipose tissue of Wistar rats fed by Fresubin (i) for 5 months, (ii) up to 90 days of age, or (iii) after 90 days of age to characterize metabolic alterations and their reversibility in rats fed with Fresubin. An intra-peritoneal glucose tolerance test was also performed to determine levels of serum leptin, adiponectin, insulin, and C-peptide in 2- and 4-month-old animals. In addition, mesenteric and epididymal adipose tissue weight, adipocyte diameter, and gene expression of pro- and anti-inflammatory adipokines and other markers were determined at the end of the study. Chronic Fresubin intake significantly increased adipocyte diameter, reduced glucose tolerance, and increased serum leptin, adiponectin, insulin, and C-peptide levels. Moreover, gene expression of leptin, adiponectin, CD68, and nuclear factor kappa B was significantly increased in mesenteric adipose tissue of Fresubin fed rats. Monocyte chemotactic protein 1 messenger RNA (mRNA) levels increased in mesenteric adipose tissue only in the group fed Fresubin during the entire experiment. In epididymal adipose tissue, fatty acid binding protein 4 mRNA levels were significantly increased in rats fed by Fresubin during adulthood. In conclusion, chronic Fresubin intake induced complex metabolic alterations in Wistar rats characteristic of metabolic syndrome. However, transition of rats from Fresubin to standard diet reversed these alterations (AU)

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Effect of chronic intake of liquid nutrition on stomach and duodenum morphology.

Changes in the quantity and/or quality of food intake have been shown to be associated with morphological and functional alterations of the gastrointestinal system. To examine this, we investigated the effect of chronic liquid nutrition intake (Fresubin) on stomach and duodenum morphology in Wistar rats fed liquid nutrition during different developmental periods. We used four groups of rats: a) control group (CON) fed pelleted chow for 130days; b) liquid nutrition group (LN) fed liquid nutrition for 130days; c) liquid nutrition juvenile group (LNJ) fed liquid nutrition for 70days and then pelleted food for 60days; d) liquid nutrition adult group (LNA) fed pelleted chow for 70days and then liquid nutrition for 60days. We found that LN and LNA rats showed a significant reduction of empty stomach mass compared to CON animals, while stomach and duodenal longitudinal muscle layer thickness did not differ between groups. Villus height was increased only in LNA animals, while villus width was increased in both LN and LNA rats. Crypt depth was reduced in LNJ. However, liquid nutrition intake did not affect villus height/crypt depth ratio, nor number of goblet cells. We found that chronic intake of liquid nutrition affects some morphological parameters of the stomach and duodenum but these changes were not homogenous between experimental groups. Interestingly, transition from liquid nutrition to solid food reversed the alterations of stomach weight as well as villus width induced by intake of liquid nutrition in LNA rats. Our data indicate that morphological and functional changes in the gastrointestinal system induced by qualitative and quantitative changes in food intake are at least partially reversible. Therefore, specific diets may be used potentially as adjuvant treatment for modulating the progression of gastrointestinal diseases by affecting stomach and small intestine morphology.

Chronic liquid nutrition intake induces obesity and considerable but reversible metabolic alterations in Wistar rats.

We have previously described the development of substantial, but reversible obesity in Wistar rats fed with palatable liquid nutrition (Fresubin). In this study, we investigated changes in serum hormone levels, glycemia, fat mass, adipocyte size, and gene expression of adipokines and inflammatory markers in adipose tissue of Wistar rats fed by Fresubin (i) for 5 months, (ii) up to 90 days of age, or (iii) after 90 days of age to characterize metabolic alterations and their reversibility in rats fed with Fresubin. An intra-peritoneal glucose tolerance test was also performed to determine levels of serum leptin, adiponectin, insulin, and C-peptide in 2- and 4-month-old animals. In addition, mesenteric and epididymal adipose tissue weight, adipocyte diameter, and gene expression of pro- and anti-inflammatory adipokines and other markers were determined at the end of the study. Chronic Fresubin intake significantly increased adipocyte diameter, reduced glucose tolerance, and increased serum leptin, adiponectin, insulin, and C-peptide levels. Moreover, gene expression of leptin, adiponectin, CD68, and nuclear factor kappa B was significantly increased in mesenteric adipose tissue of Fresubin fed rats. Monocyte chemotactic protein 1 messenger RNA (mRNA) levels increased in mesenteric adipose tissue only in the group fed Fresubin during the entire experiment. In epididymal adipose tissue, fatty acid binding protein 4 mRNA levels were significantly increased in rats fed by Fresubin during adulthood. In conclusion, chronic Fresubin intake induced complex metabolic alterations in Wistar rats characteristic of metabolic syndrome. However, transition of rats from Fresubin to standard diet reversed these alterations.

Chronic liquid nutrition feeding affects blood pressure, heart and kidney morphology, and serum lipid profile in Wistar rats.

We determined the effect of chronic liquid nutrition (Fresubin) intake in different developmental stages on the cardiovascular and renal system of male Wistar rats. Body weight, water intake and blood pressure were periodically measured. Selected serum and urine biochemical parameters reflecting metabolic and homeostatic changes after Fresubin intake were investigated as well. Heart and kidney weight, diameter of cardiomyocytes, diameter and length of cardiomyocyte nuclei, wall thickness of thoracic aorta, the diameter and the area of renal corpuscles and serum and urine biochemical parameters were assessed at the end of experiment. We showed that Fresubin intake differently affects the investigated morphological and biochemical parameters in rats and this effect was dependent on the developmental stage when Fresubin was provided. Importantly, we have shown that Fresubin-induced elevation of blood pressure is a reversible phenomenon and it is independent of weight gain and subsequent development of obesity.

Exaggerated activity of HPA axis in obese rats fed normocaloric liquid nutrition.

Experimental and clinical studies have shown alterations in activity of systems responsible for neuroendocrine stress response in obese individuals. Therefore we investigated the effect of palatable normocaloric liquid nutrition (Fresubin) on alterations in activity of the hypothalamic-pituitary-adrenal (HPA) axis in male Wistar rats of different developmental stages. Control rats (CON) received standard pellet chow all the time from weaning (21st day of age) to 150 days. Fresubin was administered throughout the experiment (LN), only in juvenility (from 21st to 90th day of age; LNJ) or only in adulthood (from 90th to 150th day of age; LNA). Body weight and energy intake were periodically monitored. Adrenal gland and fat tissue weight and plasma corticosterone levels (CORT) was determined after sacrification. Fresubin intake induced obesity in LN and LNA rats. In LN and LNA rats were observed elevated serum CORT levels, but only in LN rats with significant twofold increase compared to LNJ rats. However, the weight of adrenal glands did not differ between LN, LNJ and LNA experimental groups. Based on our results, we suggest, that obesity induced by Fresubin in LN and LNA rats is accompanied by increased HPA activity represented by elevated plasma CORT levels in these rats.

Influence of up-regulated renin-angiotensin system on the exploration, anxiety-related behavior and object recognition.

The renin-angiotensin system (RAS) plays an important role in the development of hypertension and has serious consequences on behaviour. The aim of our study was to investigate the effect of hypertension, induced by up-regulated RAS, on the exploration, anxiety-related behaviour and object recognition in laboratory rats. In the experiment, 12 weeks old normotensive Sprague-Dawley (SD) and hypertensive TGR(mREN2)27 (TGR) male rats with up-regulated RAS were used. In the open-field test, the TGR rats were less active in ambulating, rearing and sniffing and more active in self-grooming and urinating than SD ones. In the elevated plus-maze test, the TGR rats showed lower frequency of total arm entries, closed arm entries and higher frequency of defecation than in controls. In the emergence test, TGR rats did not show significant differences. In the novel object recognition task, the TGR rats spent less time with exploration of both familiar and unfamiliar objects but preferred the novel object over the familiar one and exhibited higher percentage of the total exploring time spent with novel object exploration than SD rats. Our results indicate that the TGR rats are less actively exploring, show some modifications of emotional/anxiety-related behavior and exhibited better recognition abilities.

Effect of melatonin on exploration and anxiety in normotensive and hypertensive rats with high activity of renin-angiotensin system.

OBJECTIVES: The purpose of the study was to investigate effects of melatonin (MEL) on exploration and anxiety in normotensive Sprague-Dawley (SD) and hypertensive TGR(mREN2)27 (TGR) rats with high activity of renin-angiotensin system. METHODS: Mature control (n=20) and hypertensive (n=20) rats were used. Half of each group was treated with MEL in drinking water (40 microg/ml) for 3 weeks. The influence of MEL on exploration was measured in the open field test (OF) and on anxiety in the elevated plus maze test (EPM). RESULTS: Hypertensive TGR rats showed a lower level of ambulation (p<0.05) and higher level of urination (p<0.001) in OF. In EPM they spent more time in closed arms (p<0.05) and showed low frequency of total arm entries (p<0.01) than SD rats. MEL treated SD rats exhibited increased ambulation (p<0.01), sniffing (p<0.05) and decreased creeping (p<0.05) in OF than SD controls and did not exhibit differences in behaviour observed in EPM. MEL treated TGR rats exhibited a decrease in creeping, defecation and urination (p<0.05) in OF and spent less time in closed arms (p<0.05) and increased frequency of total arm entries (p<0.05) in EPM than untreated TGR animals. CONCLUSION: Our results suggest that MEL decreased anxiety related behaviours in hypertensive rats with an up regulated renin-angiotensin system and stimulated active exploration of control animals.