Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet

Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SL versus the NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (−66%, p<0.001) and upon correction for liver weight (−44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype.

Effect of Food Predictability on Life Span in Male Mice

The purpose of this study is to compare the effect of unpredictable (U) or predictable (P) food delivery on health and longevity in mice. From 2 months of age until end of life, singly-housed male C57BL/6 mice were fed a semisynthetic diet either ad libitum (AL), or as imposed meals delivered as small pellets at either P or U times, frequencies, or amounts. The total daily food consumed by all groups was the same. The AL group gained body weight faster than either P or U groups, and had ~12% shorter median life span compared with either P or U groups. Bimonthly noninvasive body composition determinations showed that the differences in body weights were due to differences in fat and lean mass. Postmortem examinations revealed that the organ pathologies were similar in all groups, but a larger fraction of P and U mice were euthanized due to end-of-life suffering. There were no systematic differences in outcome measures between P and U groups suggesting that, within the range studied, the temporal pattern of food delivery did not have a significant metabolic effect.

Studies to Investigate the Absorption and Excretion of Shea Oleine Sterols in Rat and Man

Shea oleine (SU), an oil fraction derived from the nut of the African tree, Butyrospermum parkii, is used as a frying oil and, after hardening (SH), in margarine and toffee fat. Both SU and SH contain a high level (approximately 8%) of 4,4-dimethylsterols (4,4-DMS), mostly as esters of cinnamic acid. As part of a series of studies evaluating SU, investigations to study rat and human dietary utilization were carried out. These comprised fecal fat analysis of groups of Wistar rats and a small number (four subjects) of human volunteers. Groups of rats were administered SU in a semisynthetic diet over 3 weeks at up to 20% in the diet (approximately 10 g/kg/day). In the human study, four male volunteers consumed a single 25-g portion of SU (approximately 0.4 g/kg) and ate no other vegetable fat during the course of the study. No preferential absorption of any of the 4,4-DMS occurred in the rat or man. Apparent absorption of the most prominent sterol fraction in the unsaponifiable material, 4,4-DMS, as estimated by its disappearance from feces, was similar in both species (27% to 52% in the rat compared with 13% to 49% in human subjects). Both rats and humans showed a similar profile of dietary and fecal 4,4-DMS fraction sterol components.

Survival of Lactobacillus delbrueckiisubsp. bulgaricus and Streptococcus thermophilusin the Terminal Ileum of Fistulated Göttingen Minipigs

ABSTRACT The ability of Lactobacillus delbrueckii subsp.bulgaricus and Streptococcus thermophilusadministered in yogurt to survive the passage through the upper gastrointestinal tract was investigated with Göttingen minipigs that were fitted with ileum T-cannulas. After ingestion of yogurt containing viable microorganisms, ileostomy samples were collected nearly every hour beginning 3 h after food uptake. Living L. delbrueckii subsp. bulgaricus andS. thermophilus were detected in the magnitude of 106 to 107 per gram of intestinal contents (wet weight) in all animals under investigation. A calculation of the minimum amount of surviving bacteria that had been administered is presented. Total DNA extracted from ileostomy samples was subjected to PCR, which was species specific for L. delbrueckii andS. thermophilus and subspecies specific for L. delbrueckii subsp. bulgaricus. All three bacterial groups could be detected by PCR after yogurt uptake but not after uptake of a semisynthetic diet. One pig apparently had developed an endogenous L. delbrueckii flora. When heat-treated yogurt was administered, L. delbrueckii was detected in all animals. S. thermophilus or L. delbrueckiisubsp. bulgaricus was not detected, indicating that heat-inactivated cells and their DNAs had already been digested and their own L. delbrueckii flora had been stimulated for growth.

Vine phenological stage during larval feeding affects male and female reproductive output of Lobesia botrana (Lepidoptera: Tortricidae)

The effect of vine phenological stage during larval feeding on the reproductive output of Lobesia botrana (Denis & Schiffermüller) adults was assessed. Larvae were reared under field conditions on vine inflorescences, unripe or ripe berries simulating the first, second and third insect generations respectively. The resulting adults showed significant differences in body weight, longevity and reproductive output as measured by oviposition period, total fecundity and reproductive efficiency (viable eggs/body weight) for females, and spermatophore number and volume of the first spermatophore for males. Viable egg number was positively correlated with female body weight for all treatments but male reproductive efficiency (spermatophores/body weight) was not. The reproductive output of females from larvae reared on a standard semisynthetic diet was comparable to that of females reared on ripe berries whereas males showed a higher reproductive output when reared on semisynthetic diet. These results clearly show that data obtained from insects reared on artificial diet cannot be extrapolated to ‘field-derived’ adults. The results suggest that the variation in L. botrana reproductive output due to the larval food source should be taken into account as a potential factor affecting insect population dynamics. It is suggested that different intervention thresholds, such as those based on pheromone catches, may be needed for each of the three moth generations, to compensate for the increased fecundity and potential to cause larger amounts of crop damage of later generations.

Nota. Influencia de la pulpa y fibra natural de algarrobas sobre algunos aspectos de la utilización nutritiva de la dieta y la colesterolemia en ratas / Note. Influence of pulp and natural carob fiber on some aspects of nutritional utilization and cholesterolemia in rats

A comparative study of the influence of two subproducts from carob, its pulp (PUL) and its natural fiber (FNA), on the dietary nutritive utilization was performed. The products were included in a semisynthetic diet (50 g/kg) and administered to rats. A group of animals which consumed cellulose (CEL) was used as a control. Cholesterol levels were monitored weekly during 28 days in normal and hypercholesterolemic rats that consumed FNA and CEL (supplemented with sterols 25 g/kg diet). The intake, weight increase and food efficiency ratio (CEA) obtained were not significantly influ enced. By contrast, the fat digestibility coefficient (CDG) of the FNA group (0.97 ± 0.003) was signifi cantly lower than the corresponding CEL (0.98 ± 0.00) and PUL (0.98 ± 0.00) groups. Accordingly, the nitrogen digestibility coefficients (CDN) were significantly different: CEL, 0.93 ± 0.003; PUL, 0.91 ± 0.003, and FNA, 0.90 ± 0.003. Serum cholesterol levels were not different between the non-hypercho lesterolemic groups that consumed FNA or CEL. Concerning the evolution of the cholesterol blood level, the animals supplemented with cholesterol showed an increase that was always lower in the supplemented animals which were administered FNA compared with those that consumed CEL. This difference was statistically significant (p ≤ 0.05) in the fourth week, when the cholesterol levels of the CEL and FNA groups were 235 ± 9 mg/dL and 167 ± 12 mg/dL, respectively.