Caloric restriction increases levels of taurine in the intestine and stimulates taurine uptake by conjugation to glutathione

Our previous study indicated increased levels of taurine-conjugated bile acids (BA) in the intestine content of mice submitted to caloric restriction (CR). In the current project, we found increased levels of free taurine and taurine conjugates, including glutathione (GSH)-taurine, in CR compared to ad libitum fed animals in the mucosa along the intestine but not in the liver. The levels of free GSH were decreased in the intestine of CR compared to ad libitum fed mice. However, the levels of oxidized GSH were not affected and were complemented by the lack of changes in the antioxidative parameters. Glutathione-S transferases (GST) enzymatic activity was increased as was the expression of GST genes along the gastrointestinal tract of CR mice. In the CR intestine, addition of GSH to taurine solution enhanced taurine uptake. Accordingly, the expression of taurine transporter (TauT) was increased in the ileum of CR animals and the levels of free and BA-conjugated taurine were lower in the feces of CR compared to ad libitum fed mice. Fittingly, BA- and GSH-conjugated taurine levels were increased in the plasma of CR mice, however, free taurine remained unaffected. We conclude that CR-triggered production and release of taurine-conjugated BA in the intestine results in increased levels of free taurine what stimulates GST to conjugate and enhance uptake of taurine from the intestine.     

Consequences of rearing feeding programme on the performance of rabbit females from 1st to 2nd parturition

To evaluate how rearing programmes could affect resources allocation and reproductive performance of primiparous rabbit females, a total of 118 rabbit females were used to evaluate the effects of five rearing feeding programmes on their performance from 1st to 2nd parturition: CAL, fed ad libitum C diet (11.0 MJ digestible energy (DE), 114 g digestible protein (DP) and 358 g NDF/kg dry matter (DM) until 1st parturition; CR, fed ad libitum with C diet until 12 weeks of age and then C diet restricted (140 g/day) until 1st parturition; F, fed ad libitum with F diet (8.7 MJ DE, 88 g DP and 476 NDF/kg DM) until 1st parturition; FC, fed with F diet ad libitum until 16 weeks of age, and C diet ad libitum until 1st parturition; FCF, fed with F diet ad libitum until 16 weeks of age, then C diet ad libitum until 20 weeks and then F diet ad libitum until 1st parturition. From 1st parturition, C diet was ad libitum offered to all the experimental groups until 2nd parturition. CAL females presented lower feed intake than females of F, FC and FCF groups in the 1^st week of lactation (on av. −16.6%; P<0.05). During 1st lactation, the perirenal fat thickness change in CAL females was not different from 0 (+0.02 mm), while in the other four groups it increased (on av. +0.44 mm; P<0.05). Plasma of females fed with F diet during rearing (F, FC and FCF) had lower non-esterified fatty acids content than those exclusively fed with C diet (–0.088 and –0.072 mmol/l compared to CAL and CR, respectively; P<0.05). FCF litters had higher weight than F litters at day 21 of lactation (+247 g; P<0.05), but FCF litter had significantly lower weight than FC litters at weaning (+170 g; P<0.05). CR females had the shortest average interval between the 1st and 2nd parturition (49 days) and FCF females the longest (+ 9 days compared to CR; P<0.05). At 2nd parturition, liveborn litters of F females were larger and heavier than litters of FCF females (+2.22 kits and +138 g; P<0.05), probably due to the lower mortality at birth of F litters (–16.5 percentage points; P<0.05). In conclusion, rearing females on fibrous diets seems to increase the ability of primiparous rabbit females to obtain resources, especially at the onset of lactation.     

Effects of feeding programme on the performance and energy balance of nulliparous rabbit does

A total of 190 rabbit females were used to evaluate five feeding programmes from 9 weeks of age to the first parturition: CAL, fed ad libitum with a control diet (C: 11.0 MJ digestible energy (DE) and 114 g digestible protein (DP)/kg dry matter (DM)) until first parturition; CR, fed ad libitum with C diet until 12 weeks of age and then C diet restricted (140 g/day) until first parturition; F, fed ad libitum with a low-energy, high-fibre diet (F: 8.7 MJ DE and 88 g DP/kg DM) until first parturition; FC, fed with F diet ad libitum until 16 weeks of age, and C diet ad libitum until first parturition; FCF, fed with F diet ad libitum until 16 weeks of age, then C diet ad libitum until 20 weeks and then F diet ad libitum until first parturition. The rabbits were artificially inseminated at 18 weeks of age. CAL group had a higher mortality rate compared with the other groups between 9 and 12 weeks of age (34% v. 3%; P < 0.05) and during the last 3 weeks of first pregnancy (14% v. 3%; P < 0.05). The CAL and FC females presented higher BW and perirenal fat thickness (PFT) than CR females at 11 days of pregnancy (+0.41 kg and +0.6 mm; P < 0.05), with F females showing medium values. The type of feeding procedure did not affect the fertility rate of young females at first artificial insemination. Differences in BW disappeared at parturition, when only CAL females presented a greater PFT than CR and FC females (+0.3 mm; P < 0.05). In comparison with FCF, CAL females had smaller and thinner live born litters (−2.5 kits and −139 g, respectively; P < 0.05), with CR, F and FC females showing medium values. The low number of kits born alive for CAL females was because of their lesser total number of kits born (−1.7 kits; P < 0.05) and the greater mortality of their litters at birth (+13.9%; P < 0.05) compared with FCF females. Non-esterified fatty acid was higher in the blood of females fed C diet (CAL and CR) than in others at partum day (on average +0.15 mmol/l; P < 0.05). In conclusion, the ad libitum use of diets for lactating rabbit does throughout the rearing period could lead young rabbit females to present a higher risk of early death and smaller litter size at first parturition. Feed restriction or earlier use of suitably fibrous diets led females to achieve the critical BW and fat mass at first mating to ensure reproduction.     

Long-term calorie restriction has minimal impact on brain metabolite and fatty acid profiles in aged rats on a Western-style diet

The effect of long-term calorie restriction (CR) on metabolites, fatty acid profiles and energy substrate transporter expression in the brain was assessed in aged rats. Three groups of male Sprague–Dawley rats were studied: (i) a 2 month old ad libitum-fed (2AL group), (ii) a 19 month old ad libitum-fed (19AL group), and (iii) a 19 month old group subjected to 40% CR from the age of 7.5 to 19 months (19CR group). The diet contained high sucrose and low n-3 polyunsaturated fatty acids (PUFA) so as to imitate a Western-style diet. High resolution magic angle spinning-¹H NMR showed an effect of aging on brain cortex metabolites compared to 2AL rats, the largest differences being for myo-inositol (+251% and +181%), lactate (+203% and +188%), β-hydroxybutyrate (+176% and +618%) and choline (+148% and +120%), in 19AL and 19 CR rats, respectively. However, brain metabolites did not differ between the 19AL and 19CR groups. Cortex fatty acid profiles showed that n-3 PUFA were 35–47% lower but monounsaturated fatty acids were 40–52% higher in 19AL and 19CR rats compared to 2AL rats. Brain microvessel glucose transporter (GLUT1) was 68% higher in 19AL rats than in 2AL rats, while the monocarboxylate transporter, MCT1, was 61% lower in 19CR rats compared to 19AL rats. We conclude that on a high-sucrose, low n-3 PUFA diet, the brain of aged AL rats had higher metabolites and microvessel GLUT1 expression compared to 2AL rats. However, long-term CR in aged rats did not markedly change brain metabolite or fatty acid profile, but did reduce brain microvessel MCT1 expression.     

Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

Background

Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled.

Methods

Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5–6 consecutive days, and ad libitum intake for 1–3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)–(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding.

Results

Mice on the ID showed transient hyperphagia relative to controls during each 1–3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups.

Conclusion

Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative to energy deficit in mice.     

Effects of aging and caloric restriction on IGF-I, IGF-I receptor, IGFBP-3 and IGFBP-4 gene expression in the rat stomach and colon

The purpose of this study was to determine the effects of aging and caloric restriction (CR) on insulin-like growth factor-I (IGF-I), IGF-I receptor (IGF-IR), IGF-binding protein-3 (IGFBP-3) and IGFBP-4 expression in the stomach and colon of male Fischer 344 rats. Stomach and colonic RNA were prepared from ad libitum (AL) fed or long-term CR rats. Stomach IGF-I, IGFBP-3 and IGFBP-4 mRNA levels increased significantly (P相似文献   

Carbohydrate-restricted diet alters the gut microbiota,promotes senescence and shortens the life span in senescence-accelerated prone mice

This study examined the effects of a carbohydrate-restricted diet on aging, brain function, intestinal bacteria and the life span to determine long-term carbohydrate-restriction effects on the aging process in senescence-accelerated prone mice (SAMP8). Three-week-old male SAMP8 were divided into three groups after a week of preliminary feeding. One group was given a controlled diet, while the others fed on high-fat and carbohydrate-restricted diets, respectively. The mice in each group were further divided into two subgroups, of which one was the longevity measurement group. The other groups fed ad libitum until the mice were 50 weeks old. Before the test period termination, passive avoidance test evaluated the learning and memory abilities. Following the test period, serum and various mice organs were obtained and submitted for analysis. The carbohydrate-restricted diet group exhibited significant decrease in the survival rate as compared to the other two diet groups. The passive avoidance test revealed a remarkable decrease in the learning and memory ability of carbohydrate-restricted diet group as compared to the control-diet group. Measurement of lipid peroxide level in tissues displayed a marked increase in the brain and spleen of carbohydrate-restricted diet group than the control-diet and high-fat diet groups. Furthermore, notable serum IL-6 and IL-1β level (inflammation indicators) elevations, decrease in Enterobacteria (with anti-inflammatory action), increase in inflammation-inducing Enterobacteria and lowering of short-chain fatty acids levels in cecum were observed in the carbohydrate-restricted diet group. Hence, carbohydrate-restricted diet was revealed to promote aging and shortening of life in SAMP8.     

SIRT1 but not its increased expression is essential for lifespan extension in caloric‐restricted mice

The SIRT1 deacetylase is one of the best-studied putative mediators of some of the anti-aging effects of calorie restriction (CR), but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild-type mice on an ad libitum diet. Here, we report that median lifespan extension in CR heterozygote SIRT1^+/− mice was identical (51%) to that observed in wild-type mice, but SIRT1^+/− mice displayed a higher frequency of certain pathologies. Although larger studies in additional genetic backgrounds are needed, these results provide strong initial evidence for the requirement of SIRT1 for the lifespan extension effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension.     

Caloric restriction reduces IgA levels and modifies cytokine mRNA expression in mouse small intestine

The aim of this study was to determine the effect of caloric restriction (CR) in mouse small intestine on the production and secretion of immunoglobulin (Ig) A, the population of lymphocytes in the lamina propria, and the expression of cytokines that mediate and regulate innate and adaptive immunity. One group of young Balb/c mice was fed ad libitum, while the CR group was fed ad libitum and fasted on alternate days. When mice were six months old, IgA levels in the proximal small intestine were quantified by enzyme-linked immunosorbent assay, while the number of IgA containing cells, CD4⁺ T cells and CD8⁺ T cells in the duodenal mucosa was determined by immunohistochemistry. Furthermore, the expression of several intestinal cytokines, the genes for α-chain IgA, and the polymeric Ig receptor (pIgR) were analyzed by real-time polymerase chain reaction. CR decreased the levels of IgA in the intestine, apparently a consequence of a reduced number of IgA⁺ cells in the lamina propria that decrease the production and secretion of this Ig, and a reduced secretion of S-IgA into the bile, which in turn discharges into the proximal intestine. Contrarily, CR increased the expression of genes for α-chain IgA, and the pIgR, indicating that transport of IgA was not a key factor in the decrease of this Ig. Additionally, CR modified the expression of genes for tumor necrosis factor-α, interferon-γ, tumor growth factor-β, interleukin (IL)-2 and IL-10, all of which regulate the synthesis of IgA and pIgR, the inflammatory response, and the immune response in the intestine.     

Liquid fructose in Western-diet-fed mice impairs liver insulin signaling and causes cholesterol and triglyceride loading without changing calorie intake and body weight

Background/objectivesLiquid fructose associates with prevalence of type 2 diabetes mellitus and obesity. Intervention studies suggest that metabolically unfit individuals are more responsive than healthy individuals to liquid fructose. We determined whether mice consuming an obesogenic Western diet were more responsive than chow-fed mice to the alterations induced by liquid fructose supplementation (LFS).MethodsC57BL/6N mice were fed chow or Western diet±ad libitum 15% fructose solution for 12 weeks. Food and liquid intake and body weight were monitored. Plasma analytes and liver lipids, histology and the expression of genes related to lipid handling, endoplasmic reticulum stress, inflammation and insulin signaling were analyzed.ResultsWestern diet increased energy intake, visceral adipose tissue (vWAT), body weight, plasma and liver triglycerides and cholesterol, and inflammatory markers in vWAT vs. chow-fed mice. LFS did not change energy intake, vWAT or body weight. LFS significantly increased plasma and liver triglycerides and cholesterol levels only in Western-diet-fed mice. These changes associated with a potentiation of the increased liver expression of PPARγ and CD36 that was observed in Western-fed mice and related to the increased liver mTOR phosphorylation induced by LFS. Furthermore, LFS in Western-diet-fed mice induced the largest reduction in liver IRS2 protein and a significant decrease in whole-body insulin sensitivity.ConclusionsLFS in mice, in a background of an unhealthy diet that already induces fatty liver visceral fat accretion and obesity, increases liver lipid burden, hinders hepatic insulin signaling and diminishes whole-body insulin sensitivity without changing energy intake.     

Fat-enriched rather than high-fructose diets promote whitening of adipose tissue in a sex-dependent manner

Adipose tissue is a critical regulator of energy metabolism and an effector organ of excessive caloric intake. We studied the effects of high-fructose (HFruD), high-fat (HFD) and mixed high-sucrose and high-fat diet (HFHSD) on adipocyte morphology and biology and consecutive metabolic effects in male and female C57BL/6 mice. Forty male and 40 female mice were randomly assigned to one of four dietary groups and fed for 10 weeks ad libitum. After 10 weeks of feeding, mice were analyzed in regard to glucose metabolism, insulin sensitivity and alteration in adipocyte morphology and function. Weight gain and diminished insulin sensitivity in HFD- and HFHSD-fed mice were accompanied by increased adipocyte size and a shift in size distribution towards larger adipocytes in all mice. The latter effect was also found but less pronounced in HFruD-fed mice, while insulin sensitivity and body weight remained unaffected. In male mice, expansion of white adipocytes along with decreased uncoupling protein 1 (UCP-1) expression and alterations of mitochondrial biogenesis was found after HFD and HFHSD feeding, while in female mice, UCP-1 expression was also reduced in the HFruD dietary group. Diet-induced cellular alterations were less pronounced in female mice. Our data demonstrate that high-fat rather than high fructose consumption drives metabolically disadvantageous alterations of adipocyte differentiation involving whitening and insulin resistance in a sex-dependent manner with most deleterious effects seen upon administration of combined sucrose and fat-enriched diet in male mice.     

Obesity and weight loss result in increased adipose tissue ABCG1 expression in db/db mice

The prevalence of obesity has reached epidemic proportions and is associated with several co-morbid conditions including diabetes, dyslipidemia, cancer, atherosclerosis and gallstones. Obesity is associated with low systemic inflammation and an accumulation of adipose tissue macrophages (ATMs) that are thought to modulate insulin resistance. ATMs may also modulate adipocyte metabolism and take up lipids released during adipocyte lipolysis and cell death. We suggest that high levels of free cholesterol residing in adipocytes are released during these processes and contribute to ATM activation and accumulation during obesity and caloric restriction. Db/db mice were studied for extent of adipose tissue inflammation under feeding conditions of ad libitum (AL) and caloric restriction (CR). The major finding was a marked elevation in epididymal adipose ABCG1 mRNA levels with obesity and CR (6-fold and 16-fold, respectively) over that seen for lean wild-type mice. ABCG1 protein was also elevated for CR as compared to AL adipose tissue. ABCG1 is likely produced by cholesterol loaded ATMs since this gene is not highly expressed in adipocytes and ABCG1 expression is sterol mediated. Our data supports the concept that metabolic changes in adipocytes due to demand lipolysis and cell death lead to cholesterol loading of ATMs. Based on finding cholesterol-loaded peritoneal leukocytes with elevated levels of ABCG1 in CR as compared to AL mice, we suggest that pathways for cholesterol trafficking out of adipose tissue involve ATM egress as well as ABCG1 mediated cholesterol efflux. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).     

Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary

Background  

The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL) feeding with a group on lifespan-extending 40% calorie restriction (CR).     

Time-restricted feeding mice a high-fat diet induces a unique lipidomic profile

Time-restricted feeding (TRF) can reduce adiposity and lessen the co-morbidities of obesity. Mice consuming obesogenic high-fat (HF) diets develop insulin resistance and hepatic steatosis, but have elevated indices of long-chain polyunsaturated fatty acids (LCPUFA) that may be beneficial. While TRF impacts lipid metabolism, scant data exist regarding the impact of TRF upon lipidomic composition of tissues. We (1) tested the hypothesis that TRF of a HF diet elevates LCPUFA indices while preventing insulin resistance and hepatic steatosis and (2) determined the impact of TRF upon the lipidome in plasma, liver, and adipose tissue. For 12 weeks, male, adult mice were fed a control diet ad libitum, a HF diet ad libitum (HF-AL), or a HF diet with TRF, 12 hours during the dark phase (HF-TRF). HF-TRF prevented insulin resistance and hepatic steatosis resulting from by HF-AL treatment. TRF-blocked plasma increases in LCPUFA induced by HF-AL treatment but elevated concentrations of triacylglycerols and non-esterified saturated fatty acids. Analysis of the hepatic lipidome demonstrated that TRF did not elevate LCPUFA while reducing steatosis. However, TRF created (1) a separate hepatic lipid signature for triacylglycerols, phosphatidylcholine, and phosphatidylethanolamine species and (2) modified gene and protein expression consistent with reduced fatty acid synthesis and restoration of diurnal gene signaling. TRF increased the saturated fatty acid content in visceral adipose tissue. In summary, TRF of a HF diet alters the lipidomic profile of plasma, liver, and adipose tissue, creating a third distinct lipid metabolic state indicative of positive metabolic adaptations following HF intake.