Hyperphagia and hyperleptinemia induced by low-protein, high-carbohydrate diet is reversed at a later stage of development in rats.

This study investigated whether increased food intake after 15 days of low-protein, high-carbohydrate (LPHC) and its normalization in the later period of development change the content of key proteins related to leptin or adiponectin signaling in the hypothalamus. Male rats were divided into five groups: Control groups received a control diet (17% protein, 63% carbohydrate) for 15 (C15) or 45 (C45) days; LPHC groups received an LPHC diet (6% protein, 74% carbohydrate) for 15 (LPHC15) or 45 (LPHC45) days; and Reverse group (R): received LPHC diet for 15 days followed by control diet for another 30 days. The LPHC15 group showed increased adiposity index, leptin level, and adiponectin level, as well as decreased the leptin receptor (ObRb) and pro-opiomelanocortin (POMC) content in the hypothalamus compared with the C15 group. LPHC diet for 45 days or diet reversion (R group) rescued these alterations, except the adiponectin level in LPHC45 rats, which was higher. In summary, LPHC diet reduced hypothalamic leptin action by diminishing ObRb and POMC levels, leading to hyperphagia and adiposity body. Medium-term administration of LPHC diet or reverting to control diet restored the levels of these proteins, thereby improving body lipid mass rearrangement in adulthood.

Short-term low-protein diet during pregnancy alters islet area and protein content of phosphatidylinositol 3-kinase pathway in rats.

The phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways mediate ß cell growth, proliferation, survival and death. We investigated whether protein restriction during pregnancy alters islet morphometry or the expression and phosphorylation of several proteins involved in the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. As controls, adult pregnant and non-pregnant rats were fed a normal-protein diet (17%). Pregnant and non-pregnant rats in the experimental groups were fed a low-protein diet (6%) for 15 days. Low protein diet during pregnancy increased serum prolactin level, reduced serum corticosterone concentration and the expression of both protein kinase B/AKT1 (AKT1) and p70 ribosomal protein S6 kinase (p70S6K), as well as the islets area, but did not alter the insulin content of pancreatic islets. Pregnancy increased the expression of the Src homology/collagen (SHC) protein and the extracellular signal-regulated kinases 1/2 (ERK1/2) independent of diet. ERK1/2 phosphorylation (pERK1/2) was similar in islets from pregnant and non-pregnant rats fed a low-protein diet, and was higher in islets from pregnant rats than in islets from non-pregnant rats fed a normal-protein diet. Thus, a short-term, low-protein diet during pregnancy was sufficient to reduce the levels of proteins in the phosphatidylinositol 3-kinase pathway and affect islet morphometry.

Long-term disruption of maternal glucose homeostasis induced by prenatal glucocorticoid treatment correlates with miR-29 upregulation.

Excess of glucocorticoids (GCs) during pregnancy is strongly associated with the programming of glucose intolerance in the offspring. However, the impact of high GC levels on maternal metabolism is not clearly documented. This study aimed to test the hypothesis that mothers exposed to elevated levels of GCs might also display long-term disturbances in glucose homeostasis. Dexamethasone (DEX) was administered noninvasively to the mothers via drinking water between the 14th and the 19th days of pregnancy. Mothers were subjected to glucose and insulin tolerance tests at 1, 2, 3, 6, and 12 mo postweaning. Pregnant rats not treated with DEX and age-matched virgin rats were used as controls. Pancreatic islets were isolated at the 20th day of pregnancy and 12 mo postweaning in order to evaluate glucose-stimulated insulin secretion. The expression of the miR-29 family was also studied due to its responsiveness to GCs and its well-documented role in the regulation of pancreatic ß-cell function. Rats treated with DEX during pregnancy presented long-term glucose intolerance and impaired insulin secretion. These changes correlated with 1) increased expression of miR-29 and its regulator p53, 2) reduced expression of syntaxin-1a, a direct target of miR-29, and 3) altered expression of genes related to cellular senescence. Our data demonstrate that the use of DEX during pregnancy results in deleterious outcomes to the maternal metabolism, hallmarked by reduced insulin secretion and glucose intolerance. This maternal metabolic programming might be a consequence of time-sustained upregulation of miR-29s in maternal pancreatic islets.

Low-Protein Diet during Lactation and Maternal Metabolism in Rats.

Some metabolic alterations were evaluated in Wistar rats which received control or low-protein (17%; 6%) diets, from the pregnancy until the end of lactation: control non-lactating (CNL), lactating (CL), low-protein non-lactating (LPNL) and lactating (LPL) groups. Despite the increased food intake by LPL dams, both LP groups reduced protein intake and final body mass was lower in LPL. Higher serum glucose occurred in both LP groups. Lactation induced lower insulin and glucagon levels, but these were reduced by LP diet. Prolactin levels rose in lactating, but were impaired in LPL, followed by losses of mammary gland (MAG) mass and, a fall in serum leptin in lactating dams. Lipid content also reduced in MAG and gonadal white adipose tissue of lactating and, in LPL, contributed to a decreased daily milk production, and consequent impairment of body mass gain by LPL pups. Liver mass, lipid content and ATP-citrate enzyme activity were increased by lactation, but malic enzyme and lipid: glycogen ratio elevated only in LPL. Conclusion. LP diet reduced the development of MAG and prolactin secretion which compromised milk production and pups growth. Moreover, this diet enhanced the store of lipid to glycogen ratio and suggests a higher risk of fatty liver development.

Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice.

OBJECTIVES: We investigated the influence of leucine supplementation on insulin secretion and on some proteins related to insulin secretion in malnourished mice. METHODS: Swiss mice (aged 21 days) received isocaloric normo-17% (NP) or 6% low-protein (LP) diet for 120 days. Half of the NP and LP mice received 1.5% leucine in the drinking water during the last 30 days (NPL and LPL, respectively). RESULTS: The LP mice were hypoinsulinemic compared with the NP group, whereas LPL mice exhibited increased insulinemia in the fed state versus LP mice. The LP mouse islets were less responsive to 22.2 mM glucose, 100 microM carbachol (Cch), and 10 mM leucine than the NP group. However, LPL islets were more responsive to all these conditions compared with the LP group. The muscarinic type 3 receptor, (M3R) Cabeta2, and PKC-alpha protein contents were reduced in LP compared with NP islets but significantly higher in LPL than LP islets. The p-AKT/AKT ratio was higher in LPL compared with LP islets. CONCLUSIONS: Leucine supplementation increases insulin secretion in response to glucose and leucine and to agents that potentiate secretion, such as Cch, in malnourished mice. The enhanced levels of M3R, Cabeta2, and PKC-alpha proteins, as well as of the p-AKT/AKT ratio, may play a role in this process.

Nutritional recovery with rice bran did not modify energy balance and leptin and insulin levels.

OBJECTIVE: To investigate the effect of nutritional recovery with rice bran on energy balance, leptin and insulin levels. METHODS: Weaned Wistar rats were fed on a 17% (Control - C) or 0.5% (Aproteic - A) protein diet for 12d. After this, rats were kept on a C diet (C) or recovered with control (Recovered Control - RC) or control plus recovered rice bran diet (Recovered Rice Bran - RRB). RESULTS: Despite the increased food intake, group A exhibited lower carcass fat associated to low serum leptin. RRB and RC groups showed lower carcass weight and energy intake and expenditure. Energy expenditure was positively associated with food intake and carcass weight. Negative correlations between HOMA-IR and energy expenditure and energy intake were observed. CONCLUSION: Nutritional recovery with rice bran did not modify energy balance, leptin and insulin levels.

Nutritional recovery with rice bran did not modify energy balance and leptin and insulin levels / Recuperação nutricional com farelo de arroz não modificou o balanço energético e os níveis de leptina e insulina

OBJECTIVE: To investigate the effect of nutritional recovery with rice bran on energy balance, leptin and insulin levels. METHODS: Weaned Wistar rats were fed on a 17 percent (Control - C) or 0.5 percent (Aproteic - A) protein diet for 12d. After this, rats were kept on a C diet (C) or recovered with control (Recovered Control - RC) or control plus recovered rice bran diet (Recovered Rice Bran - RRB). RESULTS: Despite the increased food intake, group A exhibited lower carcass fat associated to low serum leptin. RRB and RC groups showed lower carcass weight and energy intake and expenditure. Energy expenditure was positively associated with food intake and carcass weight. Negative correlations between HOMA-IR and energy expenditure and energy intake were observed. CONCLUSION: Nutritional recovery with rice bran did not modify energy balance, leptin and insulin levels.

OBJETIVO: Investigar o efeito da recuperação nutricional com farelo de arroz sobre o balanço energético e níveis de leptina e insulina. MÉTODOS: Ratos Wistar recém-desmamados foram alimentados com 17 por cento (Controle - C) ou 0,5 por cento (Aproteico - A) de proteína (caseína) durante 12 dias. Em seguida, ratos permaneceram com dieta controle (C) ou foram recuperados com controle (Recuperados Controle - RC) ou controle mais 5 por cento de farelo de arroz (Recuperados com Farelo de Arroz - RFA) durante 21 dias. RESULTADOS: Apesar de a ingestão alimentar ter sido maior em A, a gordura na carcaça foi reduzida, sendo associada com menor nível de leptina. Os grupos RFA e RC tiveram redução no peso da carcaça, no gasto e ingestão de energia. O gasto energético foi correlacionado com a ingestão de alimentos e o peso da carcaça fresco. Foi observada correlação negativa entre HOMA-IR com gasto energético e com ingestão de energia. CONCLUSÃO: A recuperação nutricional com farelo de arroz não modificou o balanço energético, nem os níveis de leptina e insulina.

Soybean diet alters the insulin-signaling pathway in the liver of rats recovering from early-life malnutrition.

OBJECTIVE: We investigated if alterations in the insulin-signaling pathway could contribute to reduced hepatic glycogen levels in adult rats subjected to a protein deficiency during intrauterine life and lactation and reared through to recovery on a soybean diet. METHODS: Rats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with a 17% casein diet (offspring born to and suckled by mothers fed a control diet and subsequently fed the same diet after weaning [CC group] and offspring born to and suckled by mothers fed a control diet and subsequently fed a soybean flour diet with 17% protein after weaning [CS group]), a soybean diet (offspring of mothers fed a low-protein diet and a control diet after weaning [LC group] and offspring of mothers fed a low-protein diet and fed a soybean flour diet containing 17% protein after weaning [LS group]), or a 6% casein diet (offspring of mothers fed a low-protein diet and subsequently fed the same diet after weaning [LL group]) from weaning until 90 d of life. RESULTS: A soybean diet did not modify basal serum glucose and glucagon concentrations, but raised basal serum insulin and consequently increased the serum insulin/glucose ratio. Insulin receptor and insulin receptor substrate-1 levels were lower in rats fed a soybean diet compared with those maintained with a casein diet. In the LS group, the p85 levels were higher than in the LC group, whereas in CS rats its expression was lower than in CC rats. The expression of p110 was lower in the CS group compared with the CC group and similar in the LS and LC groups. Insulin receptor substrate-1 phosphorylation was similar in the LS, LC, and CS groups and lower compared with the CC group. The insulin receptor substrate-1-p85/phosphatidylinositol 3-kinase association was lower in LS than in LC rats and in CS than in CC rats. Akt phosphorylation was lower in the CS and LS groups than in the CC and LC groups. CONCLUSION: Adult rats maintained with a soybean diet exhibited insulin resistance due, at least in part, to alterations in the early steps of the insulin signal transduction pathway.

Effect of nutritional recovery with soybean flour diet on body composition, energy balance and serum leptin concentration in adult rats.

BACKGROUND: Malnutrition in early life is associated with obesity in adulthood and soybean products may have a beneficial effect on its prevention and treatment. This study evaluated body composition, serum leptin and energy balance in adult rats subjected to protein restriction during the intrauterine stage and lactation and recovering on a soybean flour diet. METHODS: Five groups of the Wistar strain of albino rats were used: CC, offspring born to and suckled by mothers fed a control diet and fed the same diet after weaning; CS, offspring born to and suckled by mothers fed a control diet and fed a soybean diet with 17% protein after weaning; LL, offspring of mothers fed a low protein diet and fed the same diet after weaning; LC, offspring of mothers fed a low protein diet, but fed a control diet after weaning; LS, offspring of mothers fed a low protein diet, but fed a soybean diet with 17% protein after weaning. Food intake, body, perirenal and retroperitoneal adipose tissue were measured in grams. Leptin was quantified using the Enzyme Linked Immuno Sorbent Assay (ELISA) and insulin by radioimmunoassay (RIA). Carcass composition was determined by chemical methods and energy expenditure was calculated by the difference between energy intake and carcass energy gain. Data were tested by analysis of variance (ANOVA). RESULTS: The LC and LS groups had higher energetic intake concerning body weight, lower energy expenditure, proportion of fat carcass and fat pads than CC and CS groups. The LS group showed reduced body weight gain and lower energy efficiency, which was reflected in less energy gain as protein and the proportion of carcass protein, and lower energy gain as lipid than in the LC groups, although both groups had eaten the same amount of diet and showed equal energy expenditure. Serum leptin did not differ among groups and was unrelated to food or energy intake and energy expenditure. Serum insulin was higher in the LS than in the LC group. CONCLUSION: Protein restriction during intrauterine life and lactation periods did not provoke obesity in adulthood. Nutritional recovery with soybean diet decreased the body weight at the expense of lower energy efficiency with repercussion on lean mass.

Soybean diet modulates acetyl-coenzyme A carboxylase expression in livers of rats recovering from early-life malnutrition.

OBJECTIVE: The present study evaluated the effect of nutritional recovery with a soybean diet on the gene and protein expressions and protein phosphorylation of several enzymes and transcription factors involved in hepatic lipid metabolism. METHODS: Rats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with a 17% casein (CC and LC groups) or soybean (CS and LS groups) diet and with a 6% casein (LL group) diet until 90 d of life. RESULTS: The soybean diet enhanced serum insulin levels but decreased body and liver weights and hepatic lipid and glycogen concentrations. Liver peroxisome proliferator receptor-alpha mRNA abundance was higher in the LS and CS groups than in the LC and CC groups, but the protein content was similar in all groups. Hepatic acetyl-coenzyme A carboxylase (ACC)-alpha and ACCbeta mRNA expression was markedly lower in the LS and CS rats than in the LC and CC rats. ACC protein expression was lower in the CS group than in the CC, LC, and LS groups. Phospho-[Ser(79)]2-ACC content was similar in the CS, LC, and LS groups and lower than the CC group. In the CS rats this reduction paralleled the decrease in total ACC protein. Messenger RNA and protein expression of sterol regulatory element-binding protein 1c, adenosine monophosphate-activated protein kinase, and phospho-[Thr(172)]-adenosine monophosphate-activated protein kinase was not modified by the soybean diet. CONCLUSION: Thus, the soybean diet reduced the liver lipid concentration through downregulation of the ACC gene and protein expressions rather than by phosphorylation status, which possibly resulted in decreased lipogenesis and increased beta-oxidation.

Taurine supplementation modulates glucose homeostasis and islet function.

Taurine is a conditionally essential amino acid for human that is involved in the control of glucose homeostasis; however, the mechanisms by which the amino acid affects blood glucose levels are unknown. Using an animal model, we have studied these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT). Islet cell function was determined by insulin secretion, cytosolic Ca2+ measurements and glucose metabolism from isolated islets. Islet cell gene expression and translocation was examined via immunohistochemistry and quantitative real-time polymerase chain reaction. Insulin signaling was studied by Western blot. Islets from taurine-supplemented mice had: (i) significantly higher insulin content, (ii) increased insulin secretion at stimulatory glucose concentrations, (iii) significantly displaced the dose-response curve for glucose-induced insulin release to the left, (iv) increased glucose metabolism at 5.6 and 11.1-mmol/L concentrations; (v) slowed cytosolic Ca2+ concentration ([Ca2+]i) oscillations in response to stimulatory glucose concentrations; (vi) increased insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression in the nucleus. Moreover, taurine supplementation significantly increased both basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an improved IPGTT. These results indicate that taurine controls glucose homeostasis by regulating the expression of genes required for glucose-stimulated insulin secretion. In addition, taurine enhances peripheral insulin sensitivity.

Soybean diet improves insulin secretion through activation of cAMP/PKA pathway in rats.

Maternal malnutrition leads to permanent alterations in insulin secretion of offspring and the soybean diet contributes to improve insulin release. At least a soy component, genistein, seems to increase the insulin secretion by activating the cAMP/PKA and PLC/PKC pathways. Here, we investigated the effect of the soybean diet on the expression of PKAalpha and PKCalpha, and insulin secretion in response to glucose and activators of adenylate cyclase and PKC in adult pancreatic rat islets. Rats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with 17% casein (CC and CR groups) or soybean (SC and SR groups) diet until 90 days of life. The soybean diet improved the insulin response to a physiological concentration of glucose in control islets, but only in the presence of supra-physiological concentrations of glucose in islets from CR and SR groups. PMA also improved the insulin response in islets of SC and SR groups. The expression of PKCalpha was similar in all groups. Forskolin increased the insulin secretion; however, the magnitude of the increment was lower in islets from CR and SR groups than in control animals and in those from rats maintained with soybean diet than in rats fed with casein diet. The PKAalpha expression was similar between SR and CR groups and lower in SC than in CC islets. Thus, soybean diet improved the secretory pattern of beta cells, at least in part, by activating the cAMP/PKA-signaling cascade.

Palmitic acid increase levels of pancreatic duodenal homeobox-1 and p38/stress-activated protein kinase in islets from rats maintained on a low protein diet.

A severe reduction in insulin release in response to glucose is consistently noticed in protein-deprived rats and is attributed partly to the chronic exposure to elevated levels of NEFA. Since the pancreatic and duodenal transcription factor homeobox 1 (PDX-1) is important for the maintenance of beta-cell physiology, and since PDX-1 expression is altered in the islets of rats fed a low protein (LP) diet and that rats show high NEFA levels, we assessed PDX-1 and insulin mRNA expression, as well as PDX-1 and p38/stress activated protein kinase 2 (SAPK2) protein expression, in islets from young rats fed low (6%) or normal (17%; control) protein diets and maintained for 48 h in culture medium containing 5.6 mmol/l glucose, with or without 0.6 mmol/l palmitic acid. We also measured glucose-induced insulin secretion and glucose metabolism. Insulin secretion by isolated islets in response to 16.7 mmol/l glucose was reduced in LP compared with control rats. In the presence of NEFA, there was an increase in insulin secretion in both groups. At 2.8 mmol/l glucose, the metabolism of this sugar was reduced in LP islets, regardless of the presence of this fatty acid. However, when challenged with 16.7 mmol/l glucose, LP and control islets showed a severe reduction in glucose oxidation in the presence of NEFA. The PDX-1 and insulin mRNA were significantly higher when NEFA was added to the culture medium in both groups of islets. The effect of palmitic acid on PDX-1 and p38/SAPK2 protein levels was similar in LP and control islets, but the increase was much more evident in LP islets. These results demonstrate the complex interrelationship between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis by affecting molecular mechanisms and stimulus/secretion coupling pathways.

Probiotics enhance the recovery of gut atrophy in experimental malnutrition.

AIM: The aim of this study was to evaluate the effect of probiotics on the recovery of the bowel atrophy induced by malnutrition in rats. METHODS: Twenty-and-six Wistar rats (200-250g) were fed with either a normoproteic (sham group, n=6) or a free-protein diet (n=20) during 12 days. Twelve malnourished rats were randomized to recover during 15 days with either a hydrolyzed diet (control group, n=6) or the same diet enriched with probiotics (Streptococcus thermophilus and Lactobacillus helveticus; probiotic group, n=6). RESULTS: Probiotic group showed similar gain of body, liver and bowel weight than controls. At the jejunum, both the villus height (383+/-49 vs. 321+/-46mm; p=0.04) and crypt depth (157+/-31 vs. 125+/-10mm; p=0.04) were greater in probiotic group than in controls. The crypt depth at the cecum (214+/-22 vs. 169+/-43 mm; p=0.05) and the wall width at both the cecum (410+/-18 vs. 340+/-61 mm; p=0.02) and sigmoid (479+/-130 vs. 330+/-62 mm; p=0.03) were higher in probiotic than in control group. CONCLUSION: Streptococcus thermophilus and Lactobacillus helveticus enhance the recovery of gut atrophy induced by malnutrition. Probiotics can be useful as oral adjuvants during the recovery of malnutrition.

Probiotics enhance the recovery of gut atrophy in experimental malnutrition

AIM: The aim of this study was to evaluate the effect of probiotics on the recovery of the bowel atrophy induced by malnutrition in rats. METHODS: Twenty-and-six Wistar rats (200-250 g) were fed with either a normoproteic (sham group, n=6) or a free-protein diet (n=20)during 12 days. Twelve malnourished rats were randomized to recover during 15 days with either a hydrolyzed diet (control group, n=6) or the same diet enriched with probiotics (Streptococcus thermophilus and Lactobacilus helveticus; probiotic group, n=6). RESULTS: probiotic group showed similar gain of body, liver and bowel weight than controls. At the jejunum, both thevillus height (383±49 vs. 321±46mm; p=0,04) and crypt depth (157±31 vs. 125±10mm; p=0,04) were greater in probiotic group than in controls. The crypt depth at the cecum (214±22 vs. 169±43mm; p=0,05) and the wall width at both the cecum (410±18 vs. 340±61mm; p=0,02) and sigmoid (479±130 vs. 330±62mm; p=0,03) were higher in probiotic than in control group. CONCLUSION: Streptococcus thermophillus and Lactobacillus helveticus enhance the recovery of gut atrophy induced by malnutrition. Probiotics can be useful as oral adjuvants during the recovery of malnutrition. (AU)

Probiotics enhance the recovery of gut atrophy in experimental malnutrition

AIM: The aim of this study was to evaluate the effect of probiotics on the recovery of the bowel atrophy induced by malnutrition in rats. METHODS: Twenty-and-six Wistar rats (200-250 g) were fed with either a normoproteic (sham group, n=6) or a free-protein diet (n=20)during 12 days. Twelve malnourished rats were randomized to recover during 15 days with either a hydrolyzed diet (control group, n=6) or the same diet enriched with probiotics (Streptococcus thermophilus and Lactobacilus helveticus; probiotic group, n=6). RESULTS: probiotic group showed similar gain of body, liver and bowel weight than controls. At the jejunum, both thevillus height (383±49 vs. 321±46mm; p=0,04) and crypt depth (157±31 vs. 125±10mm; p=0,04) were greater in probiotic group than in controls. The crypt depth at the cecum (214±22 vs. 169±43mm; p=0,05) and the wall width at both the cecum (410±18 vs. 340±61mm; p=0,02) and sigmoid (479±130 vs. 330±62mm; p=0,03) were higher in probiotic than in control group. CONCLUSION: Streptococcus thermophillus and Lactobacillus helveticus enhance the recovery of gut atrophy induced by malnutrition. Probiotics can be useful as oral adjuvants during the recovery of malnutrition.

Probiotics enhance recovery from malnutrition and lessen colonic mucosal atrophy after short-term fasting in rats.

OBJECTIVE: We investigated the effects of probiotics on nutritional status and gut mucosal atrophy after fasting. METHODS: Twelve rats were fasted for 3 d and then fed with rat chow (control group, n = 6) or an isoenergetic and isonitrogenous diet containing probiotics (probiotics group, n = 6; 10(6) colony-forming units/g of Bifidobacterium lactis BL and Streptococcus thermophilus) for 3 d. Twelve other rats were starved for 3 d (starved group) or normally fed with rat chow (sham group). At the end of the experiment, blood samples were collected for total protein and albumin analyses, and the colonic mucosa was weighed (in grams) and assayed for DNA content (milligrams per gram of tissue). RESULTS: Feeding efficiency was greater in the probiotic group than in the control and sham groups (P < 0.01). Animals in the probiotic group presented higher albumin than did those in the control group (P = 0.04). Colonic mucosa of the sham group (1.32 [range, 1.28-1.44]) was heavier than that of all other groups (probiotic, 1.20 [0.95-1.49], P = 0.03; control, 1.09 [0.96-1.21], P < 0.01; and starved, 1.03 [0.99-1.07], P < 0.01) and heavier in the probiotic than in the starved group (P = 0.03). The DNA content in probiotic rats (49.1 +/- 9.7) was similar to that in sham rats (53.9 +/- 5.9; P = 0.79) and higher than that in control (30.3 +/- 12.9; P = 0.01) and starved (34.4 +/- 6.5; P = 0.05) rats. CONCLUSIONS: Probiotics enhance the recovery of nutritional status and lessen gut mucosal atrophy after fasting.

Probiotics enhance the recovery of gut atrophy in experimental malnutrition.

AIM: The aim of this study was to evaluate the effect of probiotics on the recovery of the bowel atrophy induced by malnutrition in rats. METHODS: Twenty-and-six Wistar rats (200-250g) were fed with either a normoproteic (sham group, n=6) or a free-protein diet (n=20) during 12 days. Twelve malnourished rats were randomized to recover during 15 days with either a hydrolyzed diet (control group, n=6) or the same diet enriched with probiotics (Streptococcus thermophilus and Lactobacillus helveticus; probiotic group, n=6). RESULTS: Probiotic group showed similar gain of body, liver and bowel weight than controls. At the jejunum, both the villus height (383+/-49 vs. 321+/-46mm; p=0.04) and crypt depth (157+/-31 vs. 125+/-10mm; p=0.04) were greater in probiotic group than in controls. The crypt depth at the cecum (214+/-22 vs. 169+/-43 mm; p=0.05) and the wall width at both the cecum (410+/-18 vs. 340+/-61 mm; p=0.02) and sigmoid (479+/-130 vs. 330+/-62 mm; p=0.03) were higher in probiotic than in control group. CONCLUSION: Streptococcus thermophilus and Lactobacillus helveticus enhance the recovery of gut atrophy induced by malnutrition. Probiotics can be useful as oral adjuvants during the recovery of malnutrition.

Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase calpha expression.

Undernutrition has been shown to affect the autonomic nervous system, leading to permanent alterations in insulin secretion. To understand these interactions better, we investigated the effects of carbamylcholine (CCh) and phorbol 12-myristate 13-acetate (PMA) on insulin secretion in pancreatic islets from rats fed a normal (17%; NP) or low (6%; LP) protein diet for 8 wk. Isolated islets were incubated for 1 h in Krebs-bicarbonate solution containing 8.3 mmol glucose/L, with or without PMA (400 nmol/L) and CCh. Increasing concentrations of CCh (0.1-1000 micro mol/L) dose dependently increased insulin secretion by islets from both groups of rats. However, insulin secretion by islets from rats fed the NP diet was significantly higher than that of rats fed the LP diet, and the dose-response curve to CCh was shifted to the right in islets from rats fed LP with a 50% effective concentration (EC(50)) of 2.15 +/- 0.7 and 4.64 +/- 0.1 micro mol CCh/L in islets of rats fed NP and LP diets, respectively (P < 0.05). PMA-induced insulin secretion was higher in islets of rats fed NP compared with those fed LP. Western blotting revealed that the protein kinase (PK)Calpha and phospholipase (PL)Cbeta(1) contents of islets of rats fed LP were 30% lower than those of islets of rats fed NP (P < 0.05). In addition, PKCalpha mRNA expression was reduced by 50% in islets from rats fed LP. In conclusion, a reduced expression of PKCalpha and PLCbeta(1) may be involved in the decreased insulin secretion by islets from LP rats after stimulation with CCh and PMA.

Expression of PDX-1 is reduced in pancreatic islets from pups of rat dams fed a low protein diet during gestation and lactation.

Intrauterine and early postnatal malnutrition has profound consequences on fetal and postnatal development in both humans and animals. In addition, low birth weight has been reported to be associated with impaired insulin secretion, insulin resistance and diminished area of pancreatic islets. Because the transcription factor pancreatic and duodenal homeobox 1 (PDX-1) is important for the maintenance of B-cell physiology, PDX-1 expression and islet area were assessed in neonatal rats of dams fed low (6%) or normal (17%) protein diets during pregnancy. PDX-1 protein and mRNA levels, as well as insulin secretion and islet area, were measured after 28 d of life in normal, low protein and recovered rats whose dams consumed a normal protein diet after delivery. Insulin secretion by isolated islets in response to 2.8 and 16.7 mmol glucose/L was reduced in 28-d-old low protein rats compared with the control (P < 0.05). At birth and after 28 d of life, the islet area and PDX-1 protein expression were also reduced (P < 0.05). In contrast, PDX-1 mRNA levels in islets from 28-d-old low protein rats were not different from control rats. PDX-1 protein expression in pancreatic islets, the area of islets and insulin secretion were restored in recovered rats, whereas PDX-1 mRNA levels were higher than in normal rats (P < 0.05). These results suggest a link among diminished PDX-1 protein expression, a reduction in islet area and impaired insulin secretion in low protein rats. The reintroduction of a normal diet early in life restored islet area and cell physiology.