Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner.

PURPOSE: We hypothesize that different types of dietary fatty acids (FAs) affect gastrointestinal (GI) motility and visceromotor function and that this effect can be regulated by the fatty acid binding protein 4 (FABP4). METHODS: Mice were fed for 60 days with standard diet (STD), STD with 7% (by weight) coconut oil, rich in medium-chain FAs (MCFAs) (COCO), or with 7% evening primrose oil, rich in long-chain FAs (LCFAs) (EPO). In each group, half of the mice received FABP4 inhibitor, BMS309403 (1 mg/kg; i.p.) twice a week. Body weight (BW) and food intake were measured; well-established tests were performed to characterize the changes in GI motility and visceral pain. White adipose tissue and colonic samples were collected for cell culturing and molecular studies. RESULTS: COCO significantly increased GI transit, but not colonic motility. COCO and EPO delayed the onset of diarrhea, but none affected the effect of loperamide. EPO reduced BW and increased the visceromotor response (VMR) to colorectal distension (CRD). COCO and EPO reduced differentiation of preadipocytes. Treatment with BMS309403: (1) reversed the effects induced by COCO in physiological conditions and in mouse models of diarrhea; (2) prevented the effects of EPO on BW, VMR to CRD and castor oil-induced diarrhea; (3) affected proliferation of preadipocytes; (4) changed the expression of Fabp4 in colonic and adipocyte samples from COCO and EPO. CONCLUSION: Modifying dietary intake of MCFAs and LCFAs may be used to control GI motility or visceral pain and thus modulate the symptoms of functional GI disorders. The effect is dependent on the expression of FABP4.

Evaluation of insulin binding and signaling activity of newly synthesized chromium(III) complexes in vitro.

In the present study, the influence of chromium(III) complexes (acetate, chloride, glycinate, histidinate, lactate and propionate) on insulin binding and signal transduction [phosphorylation of tyrosine and serine in the insulin receptor substrate (IRS)-1] was investigated in vitro using three experimental models: isolated rat liver membranes and cultured mouse C2C12 myoblasts or 3T3-L1 preadipocytes. The examined complexes did not elevate the binding of insulin to the liver membranes. Moreover, chromium histidinate, lactate, acetate and propionate complexes diminished the specific binding of insulin. Simultaneously, chromium chloride, which did not significantly elevate insulin binding, increased the number of membrane accessible particles of the insulin receptors. However, it was accompanied by slightly diminished affinity of the receptor to the hormone. Chromium acetate and propionate significantly diminished the binding capacity of the low-affinity insulin receptor class. Investigations with the myoblast cell line C2C12 and preadipocyte cell line 3T3-L1 did not allow differentiation of the influence of the examined complexes on insulin binding. Immunodetection of phosphorylated forms of IRS-1 showed that the chromium compounds modulated the transduction of the insulin signal. Chromium glycinate, acetate and propionate decreased the amount of IRS-1 phosphorylated at serine. Since it is generally thought that phosphorylation of serine in IRS-1 may moderate insulin action, the above mentioned chromium complexes may, in this way, enhance insulin effects inside target cells. Phosphorylation of tyrosine in IRS-1, which acts as a stimulatory signal for further steps of insulin action, was elevated after the incubation of 3T3-L1 cells with insulin. Chromium supplementation did not additionally intensify this process. However, in the absence of insulin, chromium glycinate and acetate slightly elevated the level of IRS-1 phosphorylated at tyrosine. This fact may be important in vivo at low levels of insulin in blood. The results indicate that the action of chromium(III) complexes involves a direct effect on the number of receptors accessible to insulin, their affinity to the hormone and the modulation of the signal multiplying proteins by their phosphorylation.

Changes of agouti-related protein in hypothalamus, placenta, and serum during pregnancy in the rat.

Agouti-related protein (AGRP) is a homolog of the agouti protein and acts as an antagonist of peptides derived from propiomelanocortin through melanocortin receptors. This peptide is produced mainly in the hypothalamus, particularly during negative energy balance and influences increased food intake. In the hypothalamus, this peptide is co-expressed in arcuate nuclei with neuropeptide Y, another important peptide that regulates energy metabolisms. In our study, we analyzed changes in the Agrp mRNA level in the hypothalamus as well as mRNA and protein levels in placenta during different stages of rat pregnancy. We also investigated the AGRP level in the blood serum. In this study, we found the AGRP level in serum increased, while its gene expression in the hypothalamus increased only up to the 13th day of pregnancy, and decreased on the 18th day. This study demonstrates that AGRP is expressed during late pregnancy in placenta. Moreover, we found that AGRP expression is higher on the 18th than on the 13th day of pregnancy. Our results indicate that AGRP may play an important role during pregnancy in the mother's and, possibly, also in the fetus's energy balance.

Leptin and its receptors in the course of pregnancy in the rat.

Control of processes responsible for food intake and regulation of energy homeostasis during pregnancy is crucial for mother as well as for fetus development. Leptin is one of the main hormonal factors involved in regulation these processes in organisms. During pregnancy leptin regulates mother's energy balance and may also affect fetus growth and development, particularly via receptors in hypothalamus arcuate nuclei (ARC), pituitary and placenta. In the present study, serum leptin levels and expression of both short (ObRs) and long (ObRb) form of leptin receptor in the hypothalamus, pituitary and placenta were measured in the course of pregnancy. The results of these studies indicate that leptin concentration in serum increases during pregnancy and decreases 24 h after the delivery. The expression of both short and long forms of the leptin receptor in the hypothalamus decreases in the course of pregnancy and increases after the delivery. In the pituitary, however, a decrease of leptin receptor mRNA during pregnancy was observed only for ObRb. Analysis of placental leptin receptor expression demonstrated an increase of ObRb and constant high levels of ObRs mRNA. Our results suggest that changes in leptin level and its receptor expression may influence the energy homeostasis during pregnancy. In addition, changes in ObR expression are suggestive for: i) leptin resistance in the hypothalamus and pituitary; and ii) an increased leptin-dependent signaling in the placenta.