Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation on Adiposity and mRNA Expression of Energy Balance Related Genes in Obese Male Rats.

Supplementation with natural bioactive compounds has been proposed to be a complementary tool to the calorie-restricted diets and physical exercise programs used to tackle human overweight, obesity and Metabolic syndrome. Herein, we evaluated the effects of 14 weeks of calorie-restricted cafeteria diet either alone or combined with oral administration of the polyphenol oleuropein in obese adult male rats, compared with a control group fed standard chow and a group fed cafeteria diet. Animals were sacrificed at the age of 26 weeks and several tissues of interest were removed. The results showed that both dietary interventions reduced the adiposity index (p < 0.05 and p < 0.01, respectively), and specifically the abdominal fat depots (mesenteric: p < 0.01 and p < 0.01, respectively; and epididymal: both diets p < 0.001) and restored the decreased soleus skeletal muscle mass. Both interventions decreased leptin mRNA expression in mesenteric white adipose tissue (p < 0.05) and normalized hypothalamic Agrp mRNA expression compared to cafeteria-fed obese rats (p < 0.05). However, only the calorie-restricted cafeteria diet supplemented with oleuropein induced additional lower retroperitoneal adipose accretion (p < 0.05) and increased hypothalamic leptin receptor mRNA levels (p < 0.05). Experiments with female animals, at different doses and longer intervention periods, are needed to better determine the potential benefits of this dietary treatment.

Pomegranate natural extract Pomanox® positively modulates skin health-related parameters in normal and UV-induced photoaging conditions in Hs68 human fibroblast cells.

Skin photoaging is primarily caused by ultraviolet radiation and can lead to the degradation of skin extracellular matrix components, resulting in hyperpigmentation and skin elasticity loss. In this area, polyphenols have become of great interest because of their antioxidant, anti-inflammatory and antiaging properties. Here, we evaluated the effects of the pomegranate natural extract Pomanox® on skin health-related parameters in normal and UV-induced photoaging conditions in human fibroblast Hs68 cells. Moreover, the inhibitory effects of Pomanox® on tyrosinase activity were assessed. In normal conditions, Pomanox® significantly modulated collagen and hyaluronic acid metabolisms. In UV-exposed cells, both preventive and regenerative treatments with Pomanox® positively modulated hyaluronic acid metabolism and decreased ROS levels. However, only the preventive treatment modulated collagen metabolism. Finally, Pomanox® showed a marked inhibitory capacity of tyrosinase activity (IC50 = 394.7 µg/mL). The modulation of skin health-related parameters exhibited by Pomanox® open a wide range of potential applications of this product.

Behavioral and Metabolic Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation in Obese Male Rats.

Diet-induced obesity models are widely used to investigate dietary interventions for treating obesity. This study was aimed to test whether a dietary intervention based on a calorie-restricted cafeteria diet (CAF-R) and a polyphenolic compound (Oleuropein, OLE) supplementation modified sucrose intake, preference, and taste reactivity in cafeteria diet (CAF)-induced obese rats. CAF diet consists of high-energy, highly palatable human foods. Male rats fed standard chow (STD) or CAF diet were compared with obese rats fed CAF-R diet, alone or supplemented with an olive tree leaves extract (25 mg/kg*day) containing a 20.1% of OLE (CAF-RO). Biometric, food consumption, and serum parameters were measured. CAF diet increased body weight, food and energy consumption and obesity-associated metabolic parameters. CAF-R and CAF-RO diets significantly attenuated body weight gain and BMI, diminished food and energy intake and improved biochemical parameters such as triacylglycerides and insulin resistance which did not differ between CAF-RO and STD groups. The three cafeteria groups diminished sucrose intake and preference compared to STD group. CAF-RO also diminished the hedonic responses for the high sucrose concentrations compared with the other groups. These results indicate that CAF-R diet may be an efficient strategy to restore obesity-associated alterations, whilst OLE supplementation seems to have an additional beneficial effect on sweet taste function.

Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.

Blueberry consumption can prevent obesity-linked metabolic diseases, and it has been proposed that the polyphenol content of blueberries may contribute to these effects. Polyphenols have been shown to favorably impact metabolic health, but the role of specific polyphenol classes and whether the gut microbiota is linked to these effects remain unclear. We aimed to evaluate the impact of whole blueberry powder and blueberry polyphenols on the development of obesity and insulin resistance and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Sixty-eight C57BL/6 male mice were assigned to one of the following diets for 12 wk: balanced diet (Chow); high-fat, high-sucrose diet (HFHS); or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT)-rich extract, or proanthocyanidin (PAC)-rich extract. After 8 wk, mice were housed in metabolic cages, and an oral glucose tolerance test (OGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups biweekly for 8 wk, followed by an OGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC- and ANT-treated mice showed improved insulin responses during OGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity and that at least part of these beneficial effects are explained by modulation of the gut microbiota.

Cherry consumption out of season alters lipid and glucose homeostasis in normoweight and cafeteria-fed obese Fischer 344 rats.

The xenohormesis theory postulates that animals, through the consumption of chemical cues, mainly polyphenols, synthetized by plants, are able to favorably adapt to changing environmental conditions. We hypothesized that the intake of fruits with a seasonally distinctive phenotype (in terms of bioactive compounds) produced a metabolic response that depends on mammals' circannual rhythms and that fruit intake out of season can lead to a disruption in characteristic seasonal metabolism. Fischer 344 rats were chronically exposed to short (L6, 6 h light/day) and long (L18, 18 h light/day) photoperiods in order to simulate autumn and spring seasons, respectively, and were fed either a standard diet (STD) or an obesogenic cafeteria diet (CAF) and orally treated with either vehicle or 100 mg kg-1 day-1 of lyophilized sweet cherry (Prunus avium L.), a fruit consumed during long-day seasons. Cherry consumption exerted a marked photoperiod-dependent effect, inducing more changes when it was consumed out of season, which was apparent in the following observations: (a) in L6 STD-fed rats, a down-regulation of the phosphorylated (p) levels of the downstream postreceptor target of insulin Akt2 in the soleus muscle and an enhancement of fatty acid transport and ß-oxidation-related pathways, which was evidenced by increased Had gene expression (soleus) and pAMPK levels (soleus and gastrocnemius) and (b) an increase in whole-body fat oxidation and circulating levels of glucose and insulin in L6-CAF-fed obese rats. Although the pathophysiological significance of these results requires further research, our findings could contribute to highlighting the importance of the consumption of seasonal fruits to maintain optimal health.

Liver fat deposition and mitochondrial dysfunction in morbid obesity: An approach combining metabolomics with liver imaging and histology.

AIM: To explore the usefulness of magnetic resonance imaging (MRI) and spectroscopy (MRS) for assessment of non-alcoholic fat liver disease (NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesity-induced NAFLD in an observational, prospective, single-site, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described (1)H NMR-based metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from (1)H NMR spectra obtained after surgery were omitted due to technical limitations. RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, which excluded the presence of non-alcoholic steatohepatitis (NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the -CH3 peak (0.9 ppm), the -CH2- peak (1.3 ppm, mostly triglyceride) and the -CH=CH- peak (2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may help to explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients. CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose.

Ubiquitous transgenic overexpression of C-C chemokine ligand 2: a model to assess the combined effect of high energy intake and continuous low-grade inflammation.

Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.