Gérard Lecannu

Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat

Short-chain fatty acids (SCFAs) are recognized as the major anions of the large intestinal content in humans, but their effect on colonic motility is controversial. This study explores the colonic motor effect of SCFAs and their mechanisms in the rat. Colonic motility (electromyography) and transit time (plastic markers) were measured in conscious rats while SCFAs were infused into the colon, either alone or after administration of neural antagonists or immunoneutralization of circulating polypeptide YY (PYY). SCFA-induced PYY release was measured by RIA and then simulated by infusing exogenous PYY. Intracolonic infusion of 0.4 mmol/h SCFAs had no effect, whereas 2 mmol/h SCFAs reduced colonic motility (36 ± 3 vs. 57 ± 4 spike bursts/h with saline, P< 0.05) by decreasing the ratio of nonpropulsive to propulsive activity. This resulted in an increased transit rate ( P < 0.01). Neither α-adrenoceptor blockade nor nitric oxide synthase inhibition prevented SCFA-induced motility reduction. Intraluminal procaine infusion suppressed the SCFA effect, indicating that a local neural mechanism was involved. SCFA colonic infusion stimulated PYY release in blood. Immunoneutralization of circulating PYY abolished the effect of SCFAs on colonic motility, whereas exogenous PYY infusion partly reproduced this effect. SCFAs modify colonic motor patterns in the rat and increase transit rate; local nerve fibers and PYY are involved in this effect.

Childhood obesity and insulin resistance in a Yucatan mini-piglet model: putative roles of IGF-1 and muscle PPARs in adipose tissue activity and development

OBJECTIVE:To explore metabolic and cellular modifications induced during childhood obesity, in a novel animal model of obese mini-piglets.DESIGN:A total of 10 four-month old Yucatan mini-pigs were followed from prepuberty to adulthood. Animals were divided into two groups. The first one had been overfed (OF) a western-type diet and the second one had been normally fed a control recommended human-type diet (NF).MEASUREMENTS:Plasma insulin-like growth factor 1 (IGF-1), insulin, leptin, nonesterified fatty acids, triglycerides (TGs) and glucose were determined at sexual maturity and at young adulthood. Quantitative gene expressions of peroxysome-proliferator-activated receptors (PPARs), glucose transporter 4, insulin receptor, IGF-1, leptin and interleukin-6 (IL-6) in skeletal muscle, adipose tissue and liver were also measured at both stages. Adult insulin sensitivity was measured via euglycaemic–hyperinsulinaemic clamps.RESULTS:Increased body weight in adult OF pigs was associated with increased body size and low insulin sensitivity. Sexually mature OF pigs had higher IGF-1 plasma concentrations than their lean littermates (P<0.05). In the OF group, TGs and glucose were both decreased (P<0.05). Muscle PPARγ and α in OF pubescent pigs as compared to NF pigs were 11 times higher and 20 times lower, respectively (P<0.01).CONCLUSION:Obesity and insulin resistance induced by overfeeding mini-pigs during development and puberty were not associated with the cluster of metabolic modifications frequently observed in their adult littermates. Increased IGF-1 concentrations and modifications of skeletal muscle PPAR (α and γ) expressions may help the young obese pig to partially regulate its glycaemia and triglyceridaemia through an increase of fat mass, which maintains its high insulin sensitivity.

Obesity induced during sexual maturation is linked to LDL-triacylglycerols in Yucatan miniature swine.

The incidence of childhood obesity is rising dramatically throughout industrialised countries. To evaluate and study the impact of childhood obesity on lipoprotein metabolism, we developed a new animal model of premature obesity. Yucatan mini-pigs aged 4 months were studied over a 12-month period from childhood to adulthood. Animals were divided into two groups: the first group were overfed a Western misbalanced diet; the second group were normally fed a recommended human-type diet. Cholesterol and triacylglycerol concentrations in VLDL-, LDL- and HDL-lipoproteins were followed from baseline to adulthood by fast protein liquid chromatography. At 10 (the end of sexual maturation) and 16 months old (adulthood), liver, visceral and subcutaneous adipose tissues were sampled. Real-time RT-PCR was performed in order to compare apo AI, apo B, apo C-III, PPAR-alpha, insulin receptor and lipoprotein lipase gene expression between groups and ages. Differences between groups were observed only after sexual maturity. Adult overfed mini-pigs had a higher LDL-cholesterol:HDL-cholesterol ratio (P < 0.05; 0.55 (SE 0.06) for overfed v. 0.42 (SE 0.04) for normally fed pigs at the tenth month of the study). In both groups, VLDL-triacylglycerol decreased (P < 0.05). VLDL-triacylglycerol evolution in the overfed group was associated with an increase in LDL-triacylglycerol plasma concentrations (P < 0.05) after sexual maturation. LDL-triacylglycerol concentration in overfed mini-pigs went from an average of 0.28 mmol/l before sexual maturation to reach an average concentration of 0.56 mmol/l afterwards. This phenomenon has never been observed in similar studies when obesity is induced in adult mini-pigs and may represent a specific hallmark of an obesity induced during sexual maturity.

Volatile fatty acid production from lupin meal in the caecum of the rat: the role of cell wall polysaccharides and α-galactosides

The seeds of most legume species are known to induce flatus problems in man and animals. These troubles are characteristic of an extensive fermentation process leading to production of gases (H2, CH4, CO2) and short-chain fatty acids. The latter components appear to have important clinical and physiological implications. Their production, in the case of the lupin, can be attributed to α-galactosides or fibres. To dissociate short-chain fatty acid production owing to α-galactosides from that owing to fibres, a fractionation was carried out with lupin meal. Two fractions were prepared: a protein isolate (used in all the diets as a protein source) and lupin fibres. Three semi-synthetic diets containing the lupin meal (containing most of the α-galactosides of the initial seed), the isolated fibres or a mixture of these two materials, were compared in rats accustomed to these experimental diets for 4 weeks. The animals were slaughtered 4, 10 or 24 h after the beginning of their last meal and volatile fatty acids (VFA) were analysed in their caecum. Of the VFA production arising from the ingestion of lupin meals, 50% appears to be derived from non-starchy polysaccharides, and 50% from the α-galactosides.