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

Treadmill intervention attenuates the cafeteria diet-induced impairment of stress-coping strategies in young adult female rats

The current prevalence of diet-induced overweight and obesity in adolescents and adults is continuously growing. Although the detrimental biochemical and metabolic consequences of obesity are widely studied, its impact on stress-coping behavior and its interaction with specific exercise doses (in terms of intensity, duration and frequency) need further investigation. To this aim, we fed adolescent rats either an obesogenic diet (cafeteria diet, CAF) or standard chow (ST). Each group was subdivided into four subgroups according to the type of treadmill intervention as follows: a sedentary group receiving no manipulation; a control group exposed to a stationary treadmill; a low-intensity treadmill group trained at 12 m/min; and a higher intensity treadmill group trained at 17 m/min. Both the diet and treadmill interventions started at weaning and lasted for 8 weeks. Subjects were tested for anxiety-like behavior in the open field test and for coping strategies in the two-way active avoidance paradigm at week 7 and were sacrificed at week 8 for biometric and metabolic characterization. CAF feeding increased the weight gain, relative retroperitoneal white adipose tissue (RWAT %), and plasma levels of glucose, insulin, triglycerides and leptin and decreased the insulin sensitivity. Treadmill intervention partially reversed the RWAT% and triglyceride alterations; at higher intensity, it decreased the leptin levels of CAF-fed animals. CAF feeding decreased the motor activity and impaired the performance in a two-way active avoidance assessment. Treadmill intervention reduced defecation in the shuttle box, suggesting diminished anxiety. CAF feeding combined with treadmill training at 17 m/min increased the time spent in the center of the open field and more importantly, partially reversed the two-way active avoidance deficit. In conclusion, this study demonstrates that at doses that decreased anxiety-like behavior, treadmill exercise partially improved the coping strategy in terms of active avoidance behavior in the CAF-fed animals. This effect was not observed at lower doses of treadmill training

Reduction of Obesity and Insulin Resistance through Dual Targeting of VAT and BAT by a Novel Combination of Metabolic Cofactors

Obesity is an epidemic disease worldwide, characterized by excessive fat accumulation associated with several metabolic perturbations, such as metabolic syndrome, insulin resistance, hypertension, and dyslipidemia. To improve this situation, a specific combination of metabolic cofactors (MC) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) was assessed as a promising treatment in a high-fat diet (HFD) mouse model. Obese animals were distributed into two groups, orally treated with the vehicle (obese + vehicle) or with the combination of metabolic cofactors (obese + MC) for 4 weeks. Body and adipose depots weights; insulin and glucose tolerance tests; indirect calorimetry; and thermography assays were performed at the end of the intervention. Histological analysis of epidydimal white adipose tissue (EWAT) and brown adipose tissue (BAT) was carried out, and the expression of key genes involved in both fat depots was characterized by qPCR. We demonstrated that MC supplementation conferred a moderate reduction of obesity and adiposity, an improvement in serum glucose and lipid metabolic parameters, an important improvement in lipid oxidation, and a decrease in adipocyte hypertrophy. Moreover, MC-treated animals presented increased adipose gene expression in EWAT related to lipolysis and fatty acid oxidation. Furthermore, MC supplementation reduced glucose intolerance and insulin resistance, with an increased expression of the glucose transporter Glut4; and decreased fat accumulation in BAT, raising non-shivering thermogenesis. This treatment based on a specific combination of metabolic cofactors mitigates important pathophysiological characteristics of obesity, representing a promising clinical approach to this metabolic disease. Keywords: obesity; adipose tissue; insulin resistance; thermogenesis; metabolic cofactor

Changes in lysophospholipids and liver status after weight loss: the RESMENA study

Background: Obesity and comorbidities such as non-alcoholic fatty liver disease (NAFLD) are major public health burdens. Alterations in lipid metabolism are involved in hepatic diseases. The objective of this study was to assess the influence of weight loss on lysophospholipid (LP) metabolism and liver status in obese subjects as well as to provide new evidence regarding the interaction of LP metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage. Methods: Thirty-three subjects from the RESMENA (Reduction of Metabolic Syndrome in Navarra, NCT01087086) study were selected based on their Fatty Liver Index (FLI). Plasma lipid species (lysophosphatidilcholine: LPC, lysophosphatidilethanolamines: LPE and lysophosphatidylinositols: LPI specifically) were determined by LC-MS, while waist circumference (WC) and other non-invasive liver markers such as, FLI and BAAT scores as well as dietary records, anthropometrical measurements, body composition by DXA and other metabolic determinants were analyzed before and after a six-month hypocaloric nutritional intervention. Results: Computed Z-scores of total LP (LPC, LPE, and LPI) were significantly decreased after 6-months of following a hypocaloric diet. Specifically, LPC14:0, LPC15:0, LPC16:1, LPC18:4, LPC20:4, showed clear relationships with weight loss. Changes in FLI score, WC and BAAT score revealed associations with general changes in LPC score. Interestingly the BAAT score was statistically associated with the LPC score after adjustment for weight loss. Conclusion: The lipidomic LPC profile analysis revealed a generalized decrease in circulating lysophospholipids after weight loss. The involvement of particular LP in liver metabolism and obesity merit further attention, as some of these specific non-invasive liver markers were reduced independently of weight loss

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

BIOCLAIMS standard diet (BIOsd): a reference diet for nutritional physiology

Experimental replication is fundamental for practicing science. To reduce variability, it is essential to control sources of variation as much as possible. Diet is an important factor that can influence many processes and functional outcomes in studies performed with rodent models. This is especially true for, but not limited to, nutritional studies. To compare functional effects of different nutrients, it is important to use standardized, semi-purified diets. Here, we propose and describe a standard reference diet, the BIOCLAIMS standard diet. The diet is AIN-93 based, but further defined with dietary and experimental requirements taken into account that allow for experiments with bioactive food components and natural (non-expensive) labeling. This diet will be implemented by two European research consortia, Mitofood and BIOCLAIMS, to ensure inter-laboratory comparability

Intake of an Obesogenic Cafeteria Diet Affects Body Weight, Feeding Behavior, and Glucose and Lipid Metabolism in a Photoperiod-Dependent Manner in F344 Rats

We previously demonstrated that chronic exposure to different photoperiods induced marked variations in several glucose and lipid metabolism-related parameters in normoweight Fischer 344 (F344) rats. Here, we examined the effects of the combination of an obesogenic cafeteria diet (CAF) and the chronic exposure to three different day lengths (L12, 12 h light/day; L18, 18 h light/day; and L6, 6 h light/day) in this rat strain. Although no changes were observed during the first 4 weeks of adaptation to the different photoperiods in which animals were fed a standard diet, the addition of the CAF for the subsequent 7 weeks triggered profound physiologic and metabolic alterations in a photoperiod-dependent manner. Compared with L12 rats, both L6 and L18 animals displayed lower body weight gain and cumulative food intake in addition to decreased energy expenditure and locomotor activity. These changes were accompanied by differences in food preferences and by a sharp upregulation of the orexigenic genes Npy and Ghsr in the hypothalamus, which could be understood as a homeostatic mechanism for increasing food consumption to restore body weight control. L18 rats also exhibited higher glycemia than the L6 group, which could be partly attributed to the decreased pAkt2 levels in the soleus muscle and the downregulation of Irs1 mRNA levels in the gastrocnemius muscle. Furthermore, L6 animals displayed lower whole-body lipid utilization than the L18 group, which could be related to the lower lipid intake and to the decreased mRNA levels of the fatty acid transporter gene Fatp1 observed in the soleus muscle. The profound differences observed between L6 and L18 rats could be related with hepatic and muscular changes in the expression of circadian rhythm-related genes Cry1, Bmal1, Per2, and Nr1d1. Although further research is needed to elucidate the pathophysiologic relevance of these findings, our study could contribute to emphasize the impact of the consumption of highly palatable and energy dense foods regularly consumed by humans on the physiological and metabolic adaptations that occur in response to seasonal variations of day length, especially in diseases associated with changes in food intake and preference such as obesity and seasonal affective disorder

Gut microbiota profile and its association with clinical variables and dietary intake in overweight/obese and lean subjects: A cross-sectional study

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.This research was funded by the Centre for the Development of Industrial Technology (CDTI) of the Spanish Ministry of Science and Innovation, grant number CER-20191010

A Pilot Study for Metabolic Profiling of Obesity-Associated Microbial Gut Dysbiosis in Male Wistar Rats

Obesity is one of the most incident and concerning disease worldwide. Definite strategies to prevent obesity and related complications remain elusive. Among the risk factors of the onset of obesity, gut microbiota might play an important role in the pathogenesis of the disease, and it has received extensive attention because it affects the host metabolism. In this study, we aimed to define a metabolic profile of the segregated obesity-associated gut dysbiosis risk factor. The study of the metabolome, in an obesity-associated gut dysbiosis model, provides a relevant way for the discrimination on the different biomarkers in the obesity onset. Thus, we developed a model of this obesity risk factors through the transference of gut microbiota from obese to non-obese male Wistar rats and performed a subsequent metabolic analysis in the receptor rats. Our results showed alterations in the lipid metabolism in plasma and in the phenylalanine metabolism in urine. In consequence, we have identified metabolic changes characterized by: (1) an increase in DG:34:2 in plasma, a decrease in hippurate, (2) an increase in 3-HPPA, and (3) an increase in o-coumaric acid. Hereby, we propose these metabolites as a metabolic profile associated to a segregated dysbiosis state related to obesity disease