Brigitte Siliart

Liver lipid metabolism.

The liver plays a key role in lipid metabolism. Depending on species it is, more or less, the hub of fatty acid synthesis and lipid circulation through lipoprotein synthesis. Eventually the accumulation of lipid droplets into the hepatocytes results in hepatic steatosis, which may develop as a consequence of multiple dysfunctions such as alterations in beta-oxidation, very low density lipoprotein secretion, and pathways involved in the synthesis of fatty acids. In addition an increased circulating pool of non-esterified fatty acid may also to be a major determinant in the pathogenesis fatty liver disease. This review also focuses on transcription factors such as sterol-regulatory-element-binding protein-1c and peroxisome proliferator-activated receptor alpha, which promote either hepatic fatty acid synthesis or oxidation.

Restoration of the integrity of rat caeco-colonic mucosa by resistant starch, but not by fructo-oligosaccharides, in dextran sulfate sodium-induced experimental colitis.

Butyrate is recognised as efficient in healing colonic inflammation, but cannot be used as a long-term treatment. Dietary fibre that produces a high-butyrate level when fermented represents a promising alternative. We hypothesised that different types of dietary fibre do not have the same efficiency of healing and that this could be correlated to their fermentation characteristics. We compared short-chain fructo-oligosaccharides (FOS) and type 3 resistant starch (RS) in a previously described dextran sulfate sodium (DSS)-induced colitis model. Seventy-two Sprague-Dawley rats received water (control rats) or DSS (50 g DSS/l for 7 d then 30 g DSS/l for 7 (day 7) or 14 (day 14) d). The rats were fed a basal diet (BD), or a FOS or RS diet creating six groups: BD-control, BD-DSS, FOS-control, FOS-DSS, RS-control and RS-DSS. Caeco-colonic inflammatory injuries were assessed macroscopically and histologically. Short-chain fatty acids (SCFA) were quantified in caeco-colon, portal vein and abdominal aorta. At days 7 and 14, caecal and distal macroscopic and histological observations were improved in RS-DSS compared with BD-DSS and also with FOS-DSS rats. Caeco-colonic SCFA were reduced in FOS-DSS and RS-DSS groups compared with healthy controls. The amount of butyrate was higher in the caecum of the RS-DSS rats than in the BD-DSS and FOS-DSS rats, whereas distal butyrate was higher in FOS-DSS rats. Partially explained by higher luminal levels of SCFA, especially butyrate, the healing effect of RS confirms the involvement of some types of dietary fibre in inflammatory bowel disease. Moreover, the ineffectiveness of FOS underlines the importance of the type of dietary substrate.

Spontaneous hormonal variations in male cats following gonadectomy

The increased prevalence of obesity after neutering in cats is problematic in veterinary practice. Although many factors seem to be involved, the role of prolactin (PRL) and insulin-like growth factor-I (IGF-I), both implicated in adipose tissue development and glucose intolerance, should be considered. Seven male cats were castrated when 11 months old. Body weight was then recorded for 56 weeks and PRL, IGF-I and leptin assayed for 44 weeks. Body weight increased steadily but only significantly after 36 weeks. It stabilised after 44 weeks, and the cats then gained about 20% of their initial body weight. IGF-I increased rapidly and was significantly higher by week 3. PRL and leptin increased with initial peaks during the eighth and eleventh weeks, respectively. This study confirms that castration rapidly modifies the hormonal balance, partly explaining the body weight increase, and that hormonal changes precede this body weight increase. Hyperleptinaemia is apparently a consequence of excess weight.

The effects of obesity-associated insulin resistance on mRNA expression of peroxisome proliferator-activated receptor-γ target genes, in dogs

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARgamma and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARgamma, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARgamma, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARgamma expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARgamma mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.

Postprandial response of plasma insulin, amylin and acylated ghrelin to various test meals in lean and obese cats

The propensity of diets of different composition to promote obesity is a current topic in feline medicine. The effects of three meals with different protein:fat ratios on hormones (insulin, acylated ghrelin and amylin) involved in the control of food intake and glucose metabolism were compared. Five lean (two females and three males, 28.6 (sd 3.4) % body fat mass (BFM), mean body weight (BW) 4590 g) and five obese (two females and three males, 37.1 (sd 4.1) % BFM, mean BW 4670 g) adult cats were studied. Only BFM differed significantly between obese and lean cats. The cats were fed a high-protein (HP), a high-fat and a high-carbohydrate diet in a randomised cross-over design. Food intake did not differ between cats fed on the different diets, but obese cats consumed significantly more energy, expressed as per kg fat-free mass, than lean cats. After a 6-week adaptation period, a test meal was given and blood samples were collected before and 0, 30, 60 and 100 min after the meal. Baseline concentrations of glucose, amylin and acylated ghrelin were higher in obese cats than in lean cats, and obese cats showed the highest postprandial responses of glucose and amylin. The HP diet led to higher postprandial amylin concentrations than the other diets, indicating a possible effect of amino acids on beta-cell secretion. Postprandial ghrelin concentrations were unaffected by diet composition. The relationship between insulin, amylin and ghrelin secretion and their relevant roles in food intake and glucose metabolism in cats require further study.

Predominance of caecal injury in a new dextran sulphate sodium treatment in rats: histopathological and fermentative characteristics.

Objectives Cyclic administrations of dextran sulphate sodium (DSS) alternating with distilled water usually induce chronic colitis after a few weeks. In order to obtain stable chronic colitis (without recovery or relapse) in a few days, a new continuous DSS treatment was tested and characterized. Short-chain fatty acids (SCFAs), which remain poorly documented in experimental colitis, were also investigated. Methods Thirty-six Sprague–Dawley rats were treated with 5% DSS for 7 days (DI) followed by 3% DSS for 7 days (DM) or 14 days (DF). Control rats received only water. Inflammatory injuries in the caecum and the colon were assessed by macroscopic (colon length, caecum weight, damages score) and histological parameters. SCFAs (acetate, propionate, butyrate) were quantified individually in caecal, proximal and distal contents. Results Macroscopic and histological observations revealed that this continuous DSS treatment induced acute inflammation (DI) followed rapidly by chronic active colitis. The latter was uncommonly predominant in the caecum and the distal colon, and was also associated with some fermentative disturbances. Caecal SCFA concentrations decreased with DSS at DI and DM. The molar ratio of caecal butyrate increased with DSS. Acetate decreased in the colon while propionate increased. Conclusion This new DSS treatment is able to induce in a few days stable chronic inflammation with caecal and distal predominant injuries, and mild fermentative caeco-colonic alterations. This model could contribute to the study of potential anti-inflammatory effects of prebiotics.

Protein Intake Does Not Affect Insulin Sensitivity in Normal Weight Cats

Type 2 diabetes is the most common form of diabetes in cats, and genetic and environmental factors play a role in the progression of this disease (1). Obesity is one of the predominant factors. Indeed, obesity is related to insulin resistance and impaired glucose tolerance in many species. Thus, in obese insulinresistant subjects, glucose tolerance is reduced, i.e., to control glycemia, the insulin secretion must be higher than in normalweight and insulin-sensitive subjects and the insulin response to stimuli, i.e., the b cell response to glucose (2) or arginine is impaired (3). Prevention of diabetes involvesminimizing the rise in postprandial glucose concentration and insulin secretion by dietary manipulations, thus reducing the demand on the b cells to produce insulin. Several studies demonstrated that insulin sensitivity could benefit from high-protein, high-fat, and lowcarbohydrate diets in mice (4) or in genetically type 2 diabetic mice (5). In humans, low-carbohydrate diets improved diabetes (6), whereas some studies showed no effect of high-protein diets (7). The results of some studies suggest that a high-carbohydrate intake could increase glucose tolerance in humans (8). In diabetic cats, a high protein diet might reduce their insulin requirement, but clear evidence is lacking (9). The mechanism by which obesity leads to insulin resistance is not well established, but may be mediated by hormonal factors. One factor is the hepatic insulin-like growth factor-1 (IGF-1). The IGF-1 receptor has immunological, structural, and functional analogies with the insulin receptor, which could explain how IGF-1 plays an insulin-like role, especially on glucose metabolism (10) and is involved in insulin resistance. The relation between insulin sensitivity and IGF-1 levels is not clear. We and others showed that insulin resistance is accompanied by increased IGF-1 levels, resulting from higher synthesis rate of IGF-1 and lower production of IGF-1 binding proteins, leading to increased IGF-1 plasma levels (11,12). Nevertheless, others showed an inverse relation with lower IGF-1 plasma levels in insulin-resistant subjects (13). Another hormonal factor is leptin, produced by expression of the ob gene. This hormone is secreted mainly by white adipose tissue (14) as a 16-kDa peptide and binds to receptors in the hypothalamus. It plays an active role in the regulation of food intake, energy expenditure, and reproductive function. The circulating level is directly proportional to the total amount of fat in the body (15). We showed previously that cats fed a high-protein diet for 6 mo gained fat-free mass without a change in body weight (BW) (16). The effect of such a diet on plasma leptin levels is not known. The present study was conducted to compare insulin sensitivity, insulin secretion, and plasma leptin and IGF-1 in cats fed diets differing in protein and carbohydrate content.

Variations of plasma leptin in show horses during a work season

Leptin is an adipocytokine mainly expressed by adipose tissue. Secretion of leptin in healthy animals is closely related to fat mass and metabolic activity. The aim of this study was to investigate plasma leptin variations, in relation to nutritional and exercise parameters in adult show horses during a work season. EDTA-blood samples were taken at rest from 37 Iberian horses. Body weight, body condition score and fat percentage determined by ultrasonic measurement of rump fat thickness were measured. Plasma leptin was determined with a multi-species RIA kit. Linear mixed effects model was used to assess relationship between plasma leptin and other biological parameters. Plasma leptin concentration was <12.6 ng/ml (mean = 2.8 ± 1.6 ng/ml) and was significantly higher during training periods (p < 0.0001) (4.5 ± 1.7 ng/ml) than in show periods (2.0 ± 1.1 ng/ml), despite a significant increase (p < 0.0001) in energy intake. The body weight remained almost constant. The plasma leptin concentrations were significantly affected by exercise (p < 0.0001), body weight (p = 0.04) and BCS (p < 0.0001), but were not affected by percentage of fat. In conclusion, the marked decrease in leptin values observed during a period of intense (i.e. excessive) exercise could result from an adaptation to cumulative alterations in energy balance, to exercise per se or to a combination of both.