Dietary Restriction Group Research Articles

Stroke risk in treatment of type 2 diabetes in China: a 7 year retrospective cohort study

BackgroundDiabetes and stroke are leading causes of death and disability, and major public health concerns in China, which accounts for 25% of patients with diabetes worldwide. Type 2 diabetes is an independent risk factor for cerebral ischaemia and accounts for about 20% of stroke cases. We previously showed that KATP channel activation provides neuroprotection against cerebral ischaemia and that sulfonylureas blocking these channels increase the stroke risk in patients with type 2 diabetes. We aimed to further determine whether different classes of antidiabetic drugs increase the risk of stroke in Chinese patients with type 2 diabetes. MethodsIn this retrospective cohort study, we used data from medical records (Jan 1, 2008, to Dec 30, 2015) of the Endocrinology Division of the Third Affiliated Hospital of Jilin University, Jilin, China. Patients aged 32–80 years with type 2 diabetes whose blood glucose control treatment included sulfonylureas, metformin, insulin, or restricted diet were eligible for inclusion. All patients also received education on diet, exercise, blood glucose monitoring, and other aspects of diabetes management. We used χ2 test was to determine significance (p<0·05) between two sets of categorical data and Student's t-test for continuous data. To determine the overall risk, we used multivariate logistic regression with stroke occurrence as the dependent variable and hypoglycaemic drug as the independent variable. Ethics approval was granted by The Third Affiliated Hospital of Jilin University. Results1829 patients were eligible for inclusion, of whom 528 had sulfonylureas, 611 had metformin, 535 had insulin, and 155 were on a restricted diet. 55 individuals who switched to alternative therapy or were lost to follow-up were excluded, and 1774 patients were included in analysis. 116 cases of stroke were recorded: 42 in the sulfonylurea group, 29 in the metformin group, 36 in the insulin group, and nine in the restricted diet group. The risk of stroke in patients given sulfonylureas was increased by 2·65 times (95% CI 1·56–4·50) compared with those given metformin, 1·21 times (0·79–1·86) compared with those given insulin, 1·13 times (0·56–2.25) compared with those on a restricted diet, and 1·63 times (1·12–2·37) compared with all three non-sulfonylurea groups. InterpretationChinese patients with diabetes receiving sulfonylureas seem to have a higher risk of stroke than those using non-sulfonylurea antidiabetic treatments. Cardiovascular safety of antidiabetic drugs needs to be carefully assessed to improve health care and quality of life in Chinese patients with diabetes. FundingHeart and Stroke Foundation of Canada (G-13-0003069) and National Sciences and Engineering Research Council of Canada (NSERC-249962-09).

Long-term Effects of Pre and Postnatal Food Restriction in Mechanical and Structural Properties of Rat Femur

Background: During early phases of life, epigenetic factors interfere with normal growth of the individual and induce morphological and functional alterations. The aim of this study was to analyze the effects of pre and postnatal food restriction in rats, on the microstructure and mechanical properties of the rat femur bone. Methods: Food restricted male rats were from pregnant mothers maintained under daily-restricted diet pre and postnatal periods. After waning, the rats were maintained with access to milk only for 12 h until weaning. The control rats were from normal pregnant mothers feeding with free access to food and water during experimental period. Animals were sacrificed at 6 and 9 weeks of age; with femur bone submitted to 3 point bending mechanical test like indicators of biomechanical properties. After that the samples were morphometrically evaluated at electronic microscope. Results: The restricted diet group showed reductions in the body weight, width and thickness of femur bone. Statistical analysis demonstrated significant (P<0.05) changes in the evaluated parameters, showing different values for the Young modulus, ultimate load at fracture, failure (maximum breaking load), percentage of maximum deformation displacement showed decrement compared with the control rats. The data of structural measure showed that microstructure arrangement was damaged by food scarcity. Findings showed that food restriction contributed to detrimental bone structure, particularly modifying the collagen bundle and consequently inducing bone fragility in adulthood, demonstrated by the flexural diminished values. Conclusion: Nutritional conditions are determinants for the bone structure establishment, with effects persisting for a long-term period, remaining until adult life. Keywords: Bone rat, breaking resistance, development, collagen fibers, food scarcity.

Effect of Astaxanthin, Vitamin E, and Vitamin C in Combination with Calorie Restriction on Sperm Quality and Quantity in Male Rats

ABSTRACTThe aim of this study was to investigate the effect of calorie restriction and dietary antioxidant supplementation, separately or in combination, on the quality and quantity of sperm in male rats. Forty male rats were randomly allocated to four groups of 10 animals each, and fed for at least 86 days with an ad libitum diet (group 1), a restricted diet (group 2), an ad libitum diet and astaxanthin, vitamin E, and vitamin C supplements (group 3), or a restricted diet with astaxanthin, vitamin E, and vitamin C supplements (group 4). At the end of the study period, sperm count and motility were determined with a hemocytometer, and differences between the groups were analyzed by analysis of variance. In addition, total antioxidant capacity and 8-epi prostaglandin F2 alpha were measured at the beginning and end of the study period with an enzyme-linked immunosorbent assay method. After 86 days, a significantly higher sperm count was seen in group 4 compared to other groups. The percentage of immotile sperm was significantly decreased in groups 2, 3, and 4 compared to group 1. A significant increase in total antioxidant capacity was observed in group 3 (p = 0.02) and group 4 (p = 0.02) compared to groups 1 and 2. Antioxidant supplementation with or without calorie restriction had no significant effect on the serum isoprostane level in any group. Astaxanthinin, combined with vitamin E, vitamin C, and calorie restriction, was able to ameliorate, in part, infertility in male rats.

Influence of gut microecology on the pathogenesis and treatment of nonalcoholic fatty liver disease

To establish a rat model of nonalcoholic fatty liver disease (NAFLD) using high-fat diet, and to dynamically observe the influence of the changes in gut microbiota on the development and progression of NAFLD in rats during and after modeling. Sprague-Dawley rats were given high-fat diet to establish the model of NAFLD, and these rats were randomly divided into high-fat group, antibiotic pretreatment group, antibiotic treatment group, restricted diet group, and control group. The rats were sacrificed in different feeding periods, and 16sRNA fluorescent quantitative PCR was used to analyze the changes in ileocecal microbiota in rats. The liver pathological scores were determined, and enzymatic colorimetry was used to measure blood lipid level in serum and liver homogenate. The sample mean t-test was used for comparison between groups. Compared with the high-fat group, the restricted diet group showed the most significant improvements in quality of life and biochemical parameters. In the restricted diet group, the number of probiotics (Bifidobacterium and Lactobacillus) at the end of the ileum gradually increased and tended to increase over the time of intervention, and the most significant difference between this group and the high-fat group occurred at the 10th week (Bifidobacterium: 0.91±0.23 vs 0.28±0.12, P < 0.05; Lactobacillus: 0.78±0.04 vs 0.21±0.03, P < 0.05), while the number of enterococci decreased. There were no significant differences in enteric bacilli between groups (all P > 0.05). At the 10th week, the liver pathological scores in the control group, antibiotic treatment group, and restricted diet group were 1.13±1.74, 4.86±0.86, and 2.94±1.91, respectively, significantly lower than 7.09±2.03 in the high fat group (all P < 0.05). Diet structure change and antibiotic intervention can adjust gut microecology, alleviate the lesions of NAFLD, and thus provide new strategies for the prevention and treatment of NAFLD from the perspective of microecology.

Short-Term Preoperative Calorie and Protein Restriction Is Feasible in Healthy Kidney Donors and Morbidly Obese Patients Scheduled for Surgery.

Introduction. Surgery-induced oxidative stress increases the risk of perioperative complications and delay in postoperative recovery. In mice, short-term preoperative dietary and protein restriction protect against oxidative stress. We investigated the feasibility of a calorie- and protein-restricted diet in two patient populations. Methods. In this pilot study, 30 live kidney donors and 38 morbidly obese patients awaiting surgery were randomized into three groups: a restricted diet group, who received a synthetic liquid diet with 30% fewer calories and 80% less protein for five consecutive days; a group who received a synthetic diet containing the daily energy requirements (DER); and a control group. Feasibility was assessed using self-reported discomfort, body weight changes, and metabolic parameters in blood samples. Results. Twenty patients (71%) complied with the restricted and 13 (65%) with the DER-diet. In total, 68% of the patients reported minor discomfort that resolved after normal eating resumed. The mean weight loss on the restricted diet was significantly greater (2.4 kg) than in the control group (0 kg, p = 0.002), but not in the DER-diet (1.5 kg). The restricted diet significantly reduced levels of serum urea and plasma prealbumin (PAB) and retinol binding protein (RBP). Conclusions. A short-term preoperative calorie- and protein-restricted diet is feasible in kidney donors and morbidly obese patients. Compliance is high and can be objectively measured via changes in urea, PAB, and RBP levels. These results demonstrate that this diet can be used to study the effects of dietary restriction on surgery-induced oxidative stress in a clinical setting.

Carbohydrate Intake Affects Weight Loss Related Improvements in Glycemic Control: Results from a Systematic Review and Regression Analysis

ObjectiveWeight loss is shown to improve glucose control and extensive research exists on the effect of carbohydrate (CHO) intake on weight loss. However, whether or not diets varying in CHO content elicit superior improvements in glycemic control when the degree of weight loss is comparable has yet to be systematically investigated.MethodsThis systematic review and regression analysis used randomized controlled trials to assess the effects of different quantities of CHO intake during energy restriction‐induced weight loss or weight maintenance on glycemic control among overweight and obese adults. Carbohydrate intake was categorized as normal (≥45 to ≤65% of total energy intake), low (≥20 to &lt;45% of total energy intake), or restricted (utilization of a ketogenic diet, initial CHO intake &lt;50 g/d). Two researchers independently screened 1882 articles from PubMed, CINAHL, Cochrane, and Scopus databases and 44 articles (with 98 intervention groups) were included in this review. Data extracted from each intervention group included the mean percentage change of body weight and mean change of serum or plasma fasting glucose (mg/dL) and insulin (μU/mL) concentrations. A mixed model ANCOVA (SAS, version 9.3) was performed on changes in glucose or insulin separately, with percent body weight change, CHO intake level (normal, low, or restricted), and their interactions as primary predictors of interest. Other information such as mean baseline body mass index, age, percentage of female subjects, continent of study origin, study duration, and dietary fat and protein intakes were also extracted and included in the model unless multicollinearity existed among the predictors.ResultsThe mean (and range) body weight changes was −5.5% (−13 to 0%), −5.7% (−13.6 to 0.3%), and −8.5% (−12.3 to −5.9%) for the normal CHO (n=48 groups), low CHO (n=40 groups), and restricted CHO (n=10 groups) diet groups, respectively. ANCOVA analyses were only performed using results from the normal and low CHO diets. This was necessary because the range of weight change for the CHO restricted diet groups was less than half of those of the other two groups which would force extrapolation of the regression results. Among all normal and low CHO diet groups, greater energy restriction‐induced weight loss was associated with greater reductions in fasting glucose (β=0.42 mg/dL, p=0.002). Each 1% weight loss predicted a 0.42 mg/dL reduction in glucose. This association was independent of normal versus low CHO intake. The impact of weight loss on changes in insulin was dependent on dietary CHO intake. Each 1% weight loss predicted 0.21 and 0.43 μU/mL reduction of insulin in the normal and low CHO groups, respectively (p=0.04), a difference of 0.22 μU/mL.ConclusionThese findings support that for a given percentage weight loss, consuming low CHO diets predicts a greater reduction in fasting insulin concentration, consistent with improved insulin‐mediated glycemic control.Support or Funding InformationUSDA‐NIFA #2011‐38420‐20038 (WWC)

Analysis of genes that influence sheep follicular development by different nutrition levels during the luteal phase using expression profiling.

Nutrition is an important factor that regulates reproductive performance of sheep and affects follicle development. However, the correlation between nutrition and follicle development is poorly understood at the molecular level. To study its possible molecular mechanisms, we performed expression profiling of granulosa cells isolated from sheep that were fed different levels of nutrition levels during the luteal phase. To do this, ewes received a maintenance diet (M), and their estrus was synchronized by intravaginal progestogen sponges for 12days. Ewes were randomly divided into the short-term dietary-restricted group (R; 0.5×M) and the nutrient-supplemented group (S; 1.5×M). RNA samples were extracted from granulosa cells. Transcriptome libraries from each group were constructed by Illumina sequencing. Among 18468 detected genes, 170 genes were significantly differentially expressed, of which 140 genes were upregulated and 30 genes were downregulated in group S relative to group R. These genes could be candidates regulating follicular development in sheep. Gene Ontology, KEGG and clustering analyses were performed. Genes related to oocyte meiosis, such as ADCY7, were upregulated. We identified two important groups of related genes that were upregulated with improved nutrition: one group comprising the genes PTGS2, UCP2 and steroidogenic acute regulatory protein and the other group comprising interleukin-1A and interleukin-1B. The genes within each group showed similar expression patterns. Additionally, all five genes are involved in the reproduction process. Quantitative real-time PCR was performed to validate the results of expression profiling. These data in our study are an abundant genomic resource to expand the understanding of the molecular and cellular events underlying follicle development.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

A randomized controlled trial comparing a prepackaged low-residue diet with a restricted diet for colonoscopy preparation: the impact on the results of colonoscopy in adenoma detection.

This study aimed to investigate the clinical utility of a prepackaged low-residue diet (PLD) compared with a restricted diet (RD) for colonoscopic bowel preparation. A prospective randomized controlled trial was carried out with patients undergoing colonoscopy. One hundred patients were randomly assigned to PLD and RD groups. In the RD group, the patients received an information sheet containing acceptable low-residue options and instructions from the medical staff. All patients received 10ml sodium picosulphate the day before colonoscopy and 1l of polyethylene glycol with ascorbic acid (PEG-A) on the day of the colonoscopy. If the bowel preparation was not adequate, an additional PEG-A solution was given. The primary outcome was the efficacy of colonic cleansing as rated by the Boston Bowel Preparation Scale (BBPS). The additional amount of PEG-A solution, adenoma detection rate and patient tolerance were assessed as secondary outcomes. The BBPS score in the PLD group was 7.3±1.7 compared with 6.5±1.7 in the RD group. The quality of bowel preparation was significantly better in the PLD group (P<0.05). The mean amount of additional PEG-A solution in the PLD group was smaller than in the RD group (293.8±474.8 vs 444.1±625.0ml), but there was no statistical difference between the two groups. Adenoma detection rates and patient tolerance were similar in the two groups. Prepackaged low-residue diets PLD is superior to RD for bowel preparation for colonoscopy.

Intestinal morphology adjustments caused by dietary restriction improves the nutritional status during the aging process of rats

During the aging process, the body's systems change structurally and loss of function can occur. Ingesting a smaller amount of food has been considered a plausible proposal for increased longevity with the quality of life. However, the effects of dietary restriction (DR) during aging are still poorly understood, especially for organs of the digestive system. This study aimed to describe the body weight, oxidative status and possible morphological changes of the intestinal wall of rats submitted to DR during the aging process (7 to 18months old). Twelve 7-month-old male Wistar rats fed ad libitum since birth were assigned to two groups: control group (CG, n=6) fed ad libitum from 7 to 18months old; and dietary restriction group (DRG, n=6) fed 50% of the amount of chow consumed by the CG from 7 to 18months old. The body weight, feed and water intake were monitored throughout the experiment. Blood, periepididymal adipose tissue (PAT) and retroperitoneal adipose tissue (RAT), and the small intestine were collected at 18months old. The blood was collected to evaluate its components and oxidative status. Sections from the duodenum and ileum were stained with HE, PAS and AB pH2.5 for morphometric analyses of the intestinal wall components, and to count intraepithelial lymphocytes (IELs), goblet cells and cells in mitosis in the epithelium. DR rats showed a reduction in weight, naso-anal length, PAT, RAT and intestinal length; however, they consumed more water. Blood parameters indicate that the DR rats remained well nourished. In addition, they showed lower lipid peroxidation. Hypertrophy of the duodenal mucosa and atrophy of the ileal mucosa were observed. The number of goblet cells and IELs was reduced, but the mitotic index remained unaltered in both duodenum and ileum. In conclusion, 50% dietary restriction for rats from 7 to 18months old contributed to improving their nutritional parameters but, to achieve this, adjustments were required in the structure of the body weight and morphology of the small intestine.

Effects of Dietary Restriction on the Expression of Lipid Metabolism and Growth Hormone Signaling Genes in the Longissimus dorsi Muscle of Korean Cattle Steers.

This study determined the effects of dietary restriction on growth and the expression of lipid metabolism and growth hormone signaling genes in the longissimus dorsi muscle (LM) of Korean cattle. Thirty-one Korean cattle steers (average age 10.5 months) were allocated to normal (N; n = 16) or dietary restriction (DR; n = 15) groups. The feeding trial consisted of two stages: for the 8-month growing period, the DR group was fed 80% of the food intake of the normal diet, and for the 6-month growth-finishing period, the DR group was fed a DR total mixed ration with 78.4% of the crude protein and 64% of the net energy for gain of the normal diet. The LM was biopsied 5 months (period 1 [P1] at 15.5 months of age) and 14 months (period 2 [P2] at 24.5 months of age) after the start of feeding. The mRNA levels were determined using real-time polymerase chain reaction. Body weight, daily feed intake, average daily gain, and feed efficiency were lower in the DR group compared with the normal group at both P1 and P2. At P1, the lipogenic fatty acid synthase (FASN) mRNA levels were lower (p<0.05) in the DR group compared with the normal group. The DR group tended (p = 0.06) to have higher of levels of growth hormone receptor (GHR) mRNA than the normal group. At P2, the DR group tended to have lower (p = 0.06) androgen receptor (AR) mRNA levels than the normal group. In conclusion, our results demonstrate that dietary restriction partially decreases the transcription of lipogenic FASN and growth hormone signaling AR genes, but increases transcription of the GHR gene. These changes in gene transcription might affect body fat accumulation and the growth of the animals.

Su1685 Diagnostic Value of Extra-Wide-Angle-View Colonoscope in the Adenoma Detection: a Multicenter Randomized Controlled Trial

patients with previous colorectal resection, mainly for those with left colectomy. Our study is the first trial comparing two different preparations in this group of patients; therefore, larger, multicentre, randomized studies are warranted to confirm our findings. Su1684 A Randomized Controlled Trial Comparing a Prepackaged LowResidue Diet Versus a Restricted Diet for Colonoscopy Preparation Tomoaki Matsumura*, Makoto Arai, Kenichiro Okimoto, Daisuke Maruoka, Shoko Minemura, Hideaki Ishigami, Tomoo Nakagawa, Osamu Yokosuka Department of Gastroenterology and Nephrology, Chiba university, Chiba, Japan Background and Aim: An Adequate bowel preparation is essential to properly visualize the colon mucosa during a colonoscopy. Therefore, a clear liquid diet is widely used for colonoscopy preparation on the day before the procedure. However, this dietary modification may be poorly tolerated. There were some previous studies for colon cleansing comparing the clear liquids diet to a low-residue diet, but the efficacy for colonoscopy preparation by a prepackaged low-residue diet compared to a restricted diet was not investigated. The aim of this study was to investigate the clinical utility of the prepackaged low-residue diet compared to the restricted diet. Material and Methods: This is a prospective randomized controlled trial of patients undergoing screening or surveillance colonoscopy. A total 100 patients were randomly assigned for this study, 50 in each group. After exclusions, 45 patients in the prepackaged 2 meal products (a lunch and dinner) low-residue diet (PLD) group and 46 in the restricted diet (RD) group were analyzed. In the RD group, the patients was given an information sheet containing acceptable low-residue options and coached by the medical staff. All patients received a sodium picosulfate the day before colonoscopy and low-volume bowel preparation (1L PEG solution + ascorbic acid: MoviPrep ) on the day of colonoscopy. If the colon cleansing was not achieved enough, additional PEG solution was given to the patients and its amount was measured. The primary outcome was efficacy of colon cleansing, rated by the modified Boston Bowel Preparation Scale (m-BBPS: 0Z inadequate, 18Z excellent). An additional amount of PEG solution, and adenoma detection rate were assessed as secondary outcomes. This study was registered at the University Hospital Medical Information Network (UMI11979). Results: The m-BBPS score in the PLD group was 14.6 3.2, compared with 12.9 3.5 in the RD group. Bowel preparation quality was significantly higher in the PLD group (P! 0.05). The mean amount of additional PEG solution in the PLD group was smaller than the RD group (293.8 474.8 vs. 444.1 625.0 mL). However there was no statistical difference between the two groups. Adenoma detection rates were similar in the two groups (73.3% vs. 71.7%). Conclusion: A prepackaged 2 meal products low-residue diet is superior to a restricted diet for colonoscopy preparation.

Expression of melanocortin-4 receptor and agouti-related peptide mRNAs in arcuate nucleus during long term malnutrition of female ovariectomized rats.

Melanocortin-4 receptor (MC4R) and agouti-related peptide (AgRP) are involved in energy homeostasis in the rat. The aim of the present study was to evaluate the expression of MC4R and AgRP mRNAs in arcuate nucleus (ARC) during long term malnutrition of female ovariectomized rats. Ten female ovariectomized rats were divided into two equal groups (n=6) of normal and restricted diet groups. Using real-time PCR, the relative expressions (compared to controls) of MC4R and AgRP mRNAs were compared between both diet groups. The relative expression of MC4R and AgRP mRNA in the ARC of female ovariectomized rats during long term malnutrition was higher than those with normal diet (P<0.05). Changes in the relative expression level of MC4R and AgRP mRNAs during long term malnutrition of rat indicated a stimulatory role of MC4R and AgRP in regulating energy balance in ARC of rat hypothalamus.

The influence of nutrition on the insulin-like growth factor system and the concentrations of growth hormone, glucose, insulin, gonadotropins and progesterone in ovarian follicular fluid and plasma from adult female horses (Equus caballus).

BackgroundFeed intake affects the GH-IGF system and may be a key factor in determining the ovarian follicular growth rate. In fat mares, the plasma IGF-1 concentration is high with low GH and a quick follicular growth rate, in contrast to values observed in thin mares. Nothing is known regarding the long-term effects of differential feed intake on the IGF system. The objective of this experiment was to quantify IGFs, IGFBPs, GH, glucose, insulin, gonadotropin and progesterone (P4) in blood and in preovulatory follicular fluid (FF) in relation to feeding levels in mares.MethodsThree years prior to the experiment, Welsh Pony mares were assigned to a restricted diet group (R, n = 10) or a well-fed group (WF, n = 9). All mares were in good health and exhibited differences in body weight and subcutaneous fat thickness. Follicular development was scanned daily and plasma was also collected daily. Preovulatory FF was collected by ultrasound-guided follicular aspiration. Hormone levels were assayed in FF and plasma with a validated RIA.ResultsAccording to scans, the total number of follicles in group R was 53% lower than group WF. Insulin and IGF-1 concentrations were higher in WF than in R mares. GH and IGF-2 concentrations were lower in plasma from WF mares than from R mares, but the difference was not significant in FF. The IGFBP-2/IGFBP-3 ratio in FF was not affected by feeding but was dramatically increased in R mare plasma. No difference in gonadotropin concentration was found with the exception of FSH, which was higher in the plasma of R mares. On the day of puncture, P4 concentrations were not affected by feeding but were higher in preovulatory FF than in plasma.ConclusionsThe bioavailability of IGF-1 or IGF-2, represented by the IGFBP2/IGFBP3 ratio, is modified by feed intake in plasma but not in FF. These differences partially explain the variability in follicular growth observed between well-fed mares and mares on restricted diets.

Protection Against Renal Ischemia Reperfusion Injury By Dietary Restriction and Fasting Through Downregulation of Mannan-Binding Lectin.

Introduction Ischemia-reperfusion injury (IRI) remains an important problem in transplantation. We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role. Preoperative dietary restriction (DR) offers robust protection against renal IRI in mice. However, the mechanism remains to be elucidated. Therefore, we investigated the impact of DR on MBL and the role of MBL in the protective mechanism of DR. Materials and Methods Male C57Bl/6 mice were fed ad libitum (AL) or underwent 72hrs fasting (FA) or 2 weeks 30%DR (n=8/group). Protein and functional activity of serum MBL-A and -C after DR were assessed as well as liver mRNA analysis. In vivo, IRI was induced by 37 min of bilateral clamping of the renal pedicles in all three groups. After clamping, mice were sutured and part of them was reconstituted via intraperitoneal injection of 100 μg/ml of human MBL. All mice were subsequently observed for a period of 7 days. Results Assessment of mRNA showed a significant downregulation in liver MBL expression in both 30%DR and FA (p≤0.004) groups. In line with this, both MBL-A and MBL-C concentrations were significantly lower (p≤0.001) after 30% DR (A=15.4 μg/ml; C=89.4 μg/ml) and FA (A=12.4 μg/ml; C=49.5 μg/ml) compared to respectively 19.9 μg/ml MBL-A and 109.6 μg/ml MBL-C in the AL group. Furthermore, we observed a significant downregulation of lectin pathway activity in both groups. Importantly, reconstitution of MBL following reperfusion breaks DR-induced protection against renal IRI in the 30%DR group, but not in the FA group. Conclusion Dietary interventions downregulate the expression and presence of MBL. Reconstitution of MBL following reperfusion breaks DR-induced protection and strongly suggests that downregulation via the lectin pathway may be one of the mechanisms by which dietary interventions protect against renal IRI.

Mechanisms of cisplatin-induced muscle atrophy

Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue.

Controlled feeding alleviates the reduced growth associated with spawning in farmed yellowtail (Seriola quinqueradiata)

Abstract Growth initiates sexual maturation in fish but the onset of maturity also leads to a marked loss in body weight. To avoid the growth loss associated with spawning, yellowtail ( Seriola quinqueradiata ) farmers have attempted to restrict the diets of their fish stocks from winter to spring, the period just before the breeding season. This prevents reductions in body weight. In our present study, we show through endocrinological and physiological analyses of harm-cultured yellowtails that the growth of these fish can be regulated through dietary control. Our results indicate that the body weights of a diet restricted yellowtail group gradually increases through the breeding season compared with the controls. Both the body weights and folk lengths of the diet restricted group surpassed the control groups. In the spawning season, the diet restricted group had smaller gonads than the controls in both sexes. However, the gonad somatic index (GSI) rapidly increased in the control group compared with the restricted group and histological observations of the controls further indicated that the testes contained sperm, and that the female gonads contained numerous oocytes that had accumulated yolk. These findings confirm that a restriction of the diet suppresses gonad development during the yellowtail breeding season. The sex steroid hormone, 17α, 20β-diOHprog, was found to be associated with this dietary control of gametogenesis as it showed decreased levels in the restricted groups compared with the controls. To further investigate the functions of 17α, 20β-diOHprog on fish growth, this hormone was administered intraperitoneally to juvenile yellowtails. Implanted fish showed a remarkable increase in body weight compared with the control group and the lipase activities of the dorsal and ventral muscles of 17α, 20β-diOHprog-injected fish were also higher than those in the control group. We conclude from our data that the regulation of the yellowtail diet can control their growth and gametogenesis.

Dietary restriction reduces age-related degeneration of stria vascularis in the inner ear of the rat

We report here beneficial effects of life-long dietary restriction on the progression of age-associated cochlear degeneration in female Sprague–Dawley rats. Thirty-month old rats on a 70% dietary restriction were compared to ad libitum fed age-matched rats, and three-month old adult rats. As expected, aged dietary restricted rats displayed about 20% higher survival rate than age-matched rats fed ad libitum. This difference was reflected also in the auditory system. In the dietary restricted group, 73% of the subjects had preserved auditory reflexes (Preyer), and only modest degeneration of the stria vascularis of the inner ear was observed. In contrast, aged ad libitum fed animals, of which only 15% had detectable Preyer reflexes, showed a marked thinning, cellular degeneration and loss of cell processes in the stria vascularis. The extent of loss of sensory hair cells (~24%) was similar in both the aged groups, and neither group showed a significant reduction in the number of spiral ganglion neurons across adult life-span. The observations thus demonstrate that dietary restriction delays age-related degradation of the auditory system. The results provide further insights into the mechanisms of strial presbycusis.

Contribution of insulin signaling to the regulation of pancreatic beta-cell mass during the catch-up growth period in a low birth weight mouse model

Children born with low birth weight have a high risk of developing type 2 diabetes mellitus later in life. In this study, we developed a mouse model for low birth weight induced by maternal caloric restriction and investigated its effects on pancreatic β-cells. At birth, the pancreatic β-cell mass in the restricted diet group (RG) offspring was significantly lower than in the control group (CG) offspring. At 8 weeks of age, the pancreatic β-cell mass was greater in the RG offspring than in the CG offspring. RG offspring showed upregulated expression of insulin receptor substrate 2 in islets at 10 weeks of age. Moreover, the activity of insulin signaling molecules in the pancreatic β-cell mass was increased during the period of catch-up growth during the early stage of life. To investigate the effect of insulin signaling on the regulation of pancreatic β-cell mass, we generated β-cell-specific 3-phosphoinositide-dependent protein kinase 1 (PDK1) heterozygous knockout (βPDK1+/−) mice. We detected delayed catch-up growth in the β-cell mass of βPDK1+/− mice that were undernourished as fetuses. Moreover, the insulin signaling pathway was impaired in the islets of βPDK1+/− mice exposed to fetal undernutrition. These findings indicate that fetal undernutrition affects the regulation of pancreatic β-cell mass through altered insulin signaling.

Life-extending ovariectomy in grasshoppers increases somatic storage, but dietary restriction with an equivalent feeding rate does not

Reduced diet or reduced reproduction each extends lifespan in many animals. It is often thought that reduced reproduction and reduced diet may act through the same mechanisms. In grasshoppers, ovariectomy extends lifespan and reduces feeding to a level similar to that used for life extension by dietary restriction, further suggesting mechanistic overlap. Here, we measure the feeding rate of ovariectomized grasshoppers and, by manipulating feeding levels, create a sham-operated & dietary restricted group with matched daily feeding. Both groups show ~25% increased survivorship near the median age of mortality for fully fed and reproductive controls. Ovariectomy results in a doubling of fat body mass and hemolymph volume in comparison to both a feeding-matched dietary restriction group and a sham-operated & fully fed control, which do not differ from each other. Total anti-oxidant activity in the hemolymph and the skeletal muscle was unchanged upon ovariectomy or dietary restriction, so it does not appear to be a major factor in lifespan extension. Next, we measured mitochondrial counts using qPCR to determine mitochondrial cytochrome-b concentrations relative to nuclear (genomic) beta-actin. Mitochondrial counts in the ovariectomized group were lower than sham-operated and fully fed controls but not than the dietary restriction group. Last, in the fat body, transcript levels of hexamerin-90 (a hemolymph storage protein) were affected by neither ovariectomy nor dietary restriction. Hence, ovariectomy resulted in large magnitude increases in organismal storage. The matched-fed dietary restricted group differed from the ovariectomized group only in organismal storage, and not in any of the cellular parameters measured here. This study suggests that longevity via ovariectomy has distinct physiological mechanisms from longevity via dietary restriction in grasshoppers that are independent of daily feeding rate, particularly for protein and fat storage.