Interesterified palm oil promotes insulin resistance and altered insulin secretion and signaling in Swiss mice.

Interesterified fats have been used to replace trans-fat in ultra-processed foods. However, their metabolic effects are not completely understood. Hence, this study aimed to investigate the effects related to glucose homeostasis in response to interesterified palm oil or refined palm oil intake. Four-week-old male Swiss mice were randomly divided into four experimental groups and fed the following diets for 8 weeks: a normocaloric and normolipidic diet containing refined palm oil (PO group) or interesterified palm oil (IPO group); a hypercaloric and high-fat diet containing refined PO (POHF group) or interesterified PO (IPOHF group). Metabolic parameters related to body mass, adiposity and food consumption showed no significant differences. As for glucose homeostasis parameters, interesterified palm oil diets (IPO and IPOHF) resulted in higher glucose intolerance than unmodified palm oil diets (PO and POHF). Euglycemic-hyperinsulinemic clamp assessment showed a higher endogenous glucose production in the IPO group compared with the PO group. Moreover, the IPO group showed significantly lower p-AKT protein content (in the muscle and liver tissues) when compared with the PO group. Analysis of glucose-stimulated static insulin secretion (11.1 mmol/L glucose) in isolated pancreatic islets showed a higher insulin secretion in animals fed interesterified fat diets (IPO and IPOHF) than in those fed with palm oil (PO and POHF). Interesterified palm oil, including in normolipidic diets, can impair insulin signaling in peripheral tissues and increase insulin secretion by ß-cells, characterizing insulin resistance in mice.

Obesity phenotype induced by high-fat diet leads to maternal-fetal constraint, placental inefficiency, and fetal growth restriction in mice.

The aim of this study was to investigate certain parameters regarding the maternal-fetal outcomes in a diet-induced obesity model. Obese, glucose-intolerant females who were exposed to a high-fat diet prior to pregnancy had lower placental efficiency and lower birth weight pups compared to the controls. Simple linear regression analyses showed that maternal obesity disrupts the proportionality between maternal and fetal outcomes during pregnancy. Maternal obesity is correlated with fetal outcomes, perhaps because of problems with hormonal signaling and exacerbation of inflammation in the maternal metabolic environment. The maternal obese phenotype altered the thickness of the placental layer, the transport of fatty acids, and the expression of growth factors. For example, lower expression of epidermal growth factor receptor (EGFR) mRNA in the obesity-prone group may have contributed to the rupture of the placental layers, leading to adverse fetal outcomes. Furthermore, maintenance of maternal glucose homeostasis and overexpression of placental growth factor (PGF) in the obesity-resistant group likely protected the placenta and fetuses from morphological and functional damage.

Interesterified palm oil increases intestinal permeability, promotes bacterial translocation, alters inflammatory parameters and tight-junction protein genic expression in Swiss mice.

High-fat diets seem to have a negative influence on the development of obesity and the processes associated with low-grade chronic systemic inflammation. In recent years, partial hydrogenated oil, rich in trans isomers, has been associated with deleterious health effects. It has been replaced by interesterified fat (IF). However, there is no evidence whether IF ingestion can exert adverse effects on the intestinal mucosa. Thus, this study aimed to evaluate the effect of IF on the intestinal mucosa of male Swiss mice fed a normal or high-fat diet, focusing on its effects on intestinal permeability and bacterial translocation and its possible damage to the intestinal epithelium. The animals were divided into 4 groups: Control (C) and Interesterified Control (IC) groups (10 En% lipids from unmodified fat or interesterified fat, respectively) and High Fat (HF) and Interesterified High Fat (IHF) groups (45 En% lipids from unmodified fat or interesterified fat, respectively). Compare to C, the IC, HF, and IHF groups presented flattened epithelium, a shorter villi length and a lower percentage of goblet cells, less mucin 2, an increased oxidative stress and more inflammatory cells, higher IL-1ß, IL-17, and IL-23 levels. These groups also presented increased intestinal permeability and gene expression of the protein claudin 2, while JAM-A and claudin 1 gene expression was reduced. IC and IHF increased IL-6 levels while reducing occludin expression. In addition, the IC group also presented a mucosa with lesions of low intensity in the ileum, an increased mucin 5ac, TNF-α levels, and reduced occludin expression in the distal jejunum. Moreover, there was a significant increase in bacterial translocation in the IC group to blood, liver, and lungs, while HF and IHF groups presented bacterial translocation which was restricted to the mesenteric lymph nodes. In summary, our results supported the hypothesis that IF added to a normolipidic diet can be considered harmful or even worse when compared to a HF.

Acute effects of fatty acids on autophagy in NPY neurones.

High-fat diet (HFD) feeding is deleterious to hypothalamic tissue, leading to inflammation and lipotoxicity, as well as contributing to central insulin resistance. Autophagy is a process that restores cellular homeostasis by degrading malfunctioning organelles and proteins. Chronic HFD-feeding down-regulates hypothalamic autophagy. However, the effects of short-term HFD-feeding and the saturated fatty acid palmitate (PA) on hypothalamic autophagy and in neurones that express neuropeptide Y (NPY) and agouti-related peptide remains unknown. Therefore, we assessed hypothalamic autophagy after 1 and 3 days of HFD-feeding. We also injected PA i.c.v and analysed the modulation of autophagy in hypothalamic tissue. Both interventions resulted in changes in autophagy-related gene profiles without significant differences in protein content of p62 and LC3B-II, markers of the autophagy pathway. When we assessed native NPY neurones in brain slices from PA-treated animals, we observed increased levels of Atg7 and LC3B protein in response to PA treatment, indicating the induction of autophagy. We then tested the direct effects of fatty acids using the immortalised hypothalamic NPY-expressing neuronal cell model mHypoE-46. We found that PA, but not palmitoleate (PO) (a monounsaturated fatty acid), was able to induce autophagy. Co-treatment with PA and PO was able to block the PA-mediated induction of autophagy, as assessed by flow cytometry. When the de novo ceramide synthesis pathway was blocked with myriocin pre-treatment, we observed a decrease in PA-mediated induction of autophagy, although there was no change with the toll-like receptor 4 inhibitor, TAK-242. Taken together, these findings provide evidence that saturated and unsaturated fatty acids can differentially regulate hypothalamic autophagy and that ceramide synthesis may be an important mediator of those effects. Understanding the mechanisms by which dietary fats affect autophagy in neurones involved in the control of energy homeostasis will provide potential new pathways for targeting and containing the obesity epidemic.

Interesterified palm oil impairs glucose homeostasis and induces deleterious effects in liver of Swiss mice.

BACKGROUND: Interesterified fats have largely replaced the partially hydrogenated oils which are the main dietary source of trans fat in industrialized food. This process promotes a random rearrangement of the native fatty acids and the results are different triacylglycerol (TAG) molecules without generating trans isomers. The role of interesterified fats in metabolism remains unclear. We evaluated metabolic parameters, glucose homeostasis and inflammatory markers in mice fed with normocaloric and normolipidic diets or hypercaloric and high-fat diet enriched with interesterified palm oil. METHODS: Male Swiss mice were randomly divided into four experimental groups and submitted to either normolipidic palm oil diet (PO), normolipidic interesterified palm oil diet (IPO), palm oil high-fat diet (POHF) or interesterified palm oil high-fat diet (IPOHF) during an 8 weeks period. RESULTS: When compared to the PO group, IPO group presented higher body mass, hyperglycemia, impaired glucose tolerance, evidence of insulin resistance and greater production of glucose in basal state during pyruvate in situ assay. We also observed higher protein content of hepatic PEPCK and increased cytokine mRNA expression in the IPO group when compared to PO. Interestingly, IPO group showed similar parameters to POHF and IPOHF groups. CONCLUSION: The results indicate that substitution of palm oil for interesterified palm oil even on normocaloric and normolipidic diet could negatively modulate metabolic parameters and glucose homeostasis as well as cytokine gene expression in the liver and white adipose tissue. This data support concerns about the effects of interesterified fats on health and could promote further discussions about the safety of the utilization of this unnatural fat by food industry.

Dietary Patterns Associated to Clinical Aspects in Crohn's Disease Patients.

Diet is an important factor in both the pathogenesis and in the clinical course of Crohn's disease (CD). However, data on dietary patterns of CD patients are rather limited in the literature. This cross-sectional study included 60 patients with CD, aged 18-60 years. Dietary intake was assessed using a validated food frequency questionnaire to measure food consumption patterns by principal component analysis (PCA). Multiple regression analysis was performed to investigate the association between dietary patterns and clinical and demographic variables. Three dietary patterns were identified: "Traditional + FODMAP" was associated with symptoms, gender, previous surgeries, and duration of the disease. "Fitness style" was positively associated with physical activity and negatively associated with body mass index and smoking. "Snacks and processed foods" was positively associated with duration of the disease and negatively associated with age. According to the weekly food consumption analysis, patients with active disease consumed less coffee and tea. We found significant associations between the three dietary patterns and the variables, but not with the stage of the disease. Prospective studies are necessary to determine the effects of food consumption patterns on the clinical course of CD.

Interesterified soybean oil promotes weight gain, impaired glucose tolerance and increased liver cellular stress markers.

Interesterified fats have largely replaced hydrogenated vegetable fat, which is rich in trans fatty acids, in the food industry as an economically viable alternative, generating interest to study their health effects. The aim of this study was to evaluate the effect that interesterification of oils and fat has on lipid-induced metabolic dysfunction, hepatic inflammation and ER stress. Five week-old male Wistar rats were randomly divided into three experimental groups, submitted to either normocaloric and normolipidic diet containing 10% of lipids from unmodified soybean oil (SO) or from interesterified soybean oil (ISO), and one more group submitted to a high fat diet (HFD) containing 60% of fat from lard as a positive control, for 8 or 16 weeks. Metabolic parameters and hepatic gene expression were evaluated. The HFD consumption led to increased body mass, adiposity and impaired glucose tolerance compared to SO and ISO at both time points of diet. However, the ISO group showed an increased body mass gain, retroperitoneal WAT mass, fasting glucose, and impaired glucose tolerance during ipGTT at 16 weeks compared to SO. Moreover, at 8 weeks, hepatic gene expression of Atf3 and Tnf were increased in the ISO group compared to the SO group. Thus, replacement of natural fat with interesterified fat on a normocaloric and normolipidic diet negatively modulated metabolic parameters and resulted in impaired glucose tolerance in rats.