Physiological responses and microbiota shifts after spermidine administration as a postbiotic on rodents fed a high-fat high-fructose diet.

The consumption of a high-fat high-fructose diet partly resemble the western dietary patterns, which is closely associated with excessive body adiposity and metabolic disorders, such as obesity and type 2 diabetes. Moreover, this unhealthy regime produces unfavourable changes on the faecal microbiota, potentially interfering with microorganisms postbiotic function, such as spermidine, a natural polyamine that has been involved in the control of weight gain. The study aimed to analyse the repercussions of spermidine supplementation on somatic measurements, metabolic markers, and the faecal microbiota profile of rats fed a diet rich in fat and fructose. Indeed, Wistar males with oral administration of spermidine (20 mg/kg/day) for 6 weeks were evaluated for food and energy intake, biochemical markers, and faecal microbiota signatures. The daily use of spermidine decreased weight gain ( P < 0.01), reduced feed efficiency ( P < 0.01), and attenuated visceral fat deposition ( P < 0.01), although no effect on energy intake, hepatic weight, triglyceride and glucose index and atherogenic indexes. Similarly, the consumption of spermidine partially restored the presence of microbial species, notably Akkermansia muciniphila. Elevated concentrations of this species were linked to a decrease in triglycerides ( P = 0.04), indicating that the supplementation of spermidine might contribute to managing energy fuel homeostasis in association with an obesogenic diet.

EFECTOS DE DIETAS RICAS EN FRUCTOSA AÑADIDA EN LA PATOGÉNESIS DEL HÍGADO GRASO NO ALCOHÓLICO / EFFECTS OF DIETS RICH IN ADDED FRUCTOSE ON THE PATHOGENESIS OF NON-ALCOHOLIC FATTY LIVER DISEASE

Introducción: El hígado graso no alcohólico se enmarca en un grupo de patologías de etiología multifactorial, en el que la alimentación tendría un papel protagónico. En este sentido, el consumo de dietas ricas en fructosa, en especial a partir de fructosa añadida o jarabe de maíz alto en fructosa, ha sido motivo de investigación por su probable rol en la patogénesis de esta enfermedad. Metodología: Se realizó una búsqueda de artículos en relación con los efectos de las dietas ricas en fructosa sobre parámetros que podrían afectar la esteatosis hepática con el objetivo de organizar las principales evidencias al respecto. Resultados: Los estudios analizados tienden a evidenciar asociaciones positivas entre estas dietas y un mayor riesgo de desarrollar disbiosis intestinal, pérdida de integridad de la barrera intestinal y esteatosis hepática. Conclusiones: Los antecedentes recopilados en la presente revisión muestran evidencia de que este tipo de dietas favorecerían una serie de eventos que pueden conducir al hígado graso no alcohólico; por lo tanto, procurar un consumo adecuado de este monosacárido representaría una interesante alternativa de prevención para esta patología

Introduction: The non-alcoholic fatty liver disease falls within the group of multifactorial etiology pathologies in which food would play an important role. It is in this regard that the consumption of diets rich in fructose, especially from added fructose or corn syrup in fructose, has been a subject of investigation due to its likely roll in the pathogenesis of this disease. Methodology: A research for articles was performed about the effects of very rich fructose diets on parameters who could affect the liver steatosis in order to organize the main evidences. Results: The studies analized tend to report positive association between this diets and a higher risk of intestinal dysbiosis, intestinal barrier loss and partially with increased hepatic steatosis. Conclusions: The records compiled in the present review show evidence that this type of diets promote a serie of events that could result in non-alcoholic fatty liver disease so try a adequate consumption of this monosaccharides it would represent an interesting alternative to prevent this pathology

Can Diet Alter the Intestinal Barrier Permeability in Healthy People? A Systematic Review.

Dietary factors can modify the function of the intestinal barrier, causing permeability changes. This systematic review analyzed evidence on the link between diet or dietary interventions and changes in intestinal barrier permeability (IBP) in healthy individuals. A systematic search for primary studies was conducted using the virtual databases EMBASE, PubMed, Web of Science, CINAHL, and Scopus. This review adhered to PRISMA 2020 guidelines, assessing the methodological quality using the Newcastle-Ottawa scale for observational studies and ROB 2.0 for randomized clinical trials. Out of 3725 studies recovered, 12 were eligible for review. Chicory inulin and probiotics reduced IBP in adults with a moderate GRADE level of evidence. The opposite result was obtained with fructose, which increased IBP in adults, with a very low GRADE level of evidence. Only intervention studies with different dietary components were found, and few studies evaluated the effect of specific diets on the IBP. Thus, there was no strong evidence that diet or dietary interventions increase or decrease IBP in healthy individuals. Studies on this topic are necessary, with a low risk of bias and good quality of evidence generated, as there is still little knowledge on healthy populations.

Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats.

INTRODUCTION: We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS. MATERIALS AND METHODS: Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. RESULTS: MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton. CONCLUSION: A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

Peripheral inflammatory hyperalgesia is exacerbated in rats with metabolic disorders induced by a fructose diet.

This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with the von Frey test and measuring paw edema to assess inflammatory responses. Wistar rats were administered water or 10% fructose solution ad libitum over a period of 5 weeks. After intraplantar administration of inflammatory agents such as carrageenan (1 mg/paw), lipopolysaccharide (LPS; 100 µg/paw), or prostaglandin E2 (PGE2, 100 ng/paw), we conducted mechanical hyperalgesia tests and paw edema evaluations. The fructose diet resulted in dyslipidemia, elevated insulin and leptin plasma levels, insulin resistance, and increased epididymal and retroperitoneal adiposity compared to control animals. In response to inflammatory agents, the fructose group displayed significantly enhanced peripheral hyperalgesia and more pronounced paw edema. Our results demonstrate that fructose not only contributes to the development of obesity and metabolic disorder but also exacerbates peripheral inflammatory pain responses by enhancing prostaglandin sensitivity.

Pregestational fructose-induced metabolic syndrome in Wistar rats causes sexually dimorphic behavioral changes in their offspring.

Metabolic syndrome (MetS), marked by enduring metabolic inflammation, has detrimental effects on cognitive performance and brain structure, influencing behavior. This study aimed to investigate whether maternal MetS could negatively impact the neurodevelopment and metabolism of offspring. To test this hypothesis, 2 months old female Wistar rats were subjected to a 10-week regimen of tap water alone or supplemented with 20% fructose to induce MetS. Dams were mated with healthy males to generate litters: OC (offspring from control dams) and OMetS (offspring from dams with MetS). To isolate prenatal effects, all pups were breastfed by control nurse dams, maintaining a standard diet and water ad libitum until weaning. Behavioral assessments were conducted between postnatal days (PN) 22 and 95, and metabolic parameters were analyzed post-sacrifice on PN100. Results from the elevated plus maze, the open field, and the marble burying tests revealed a heightened anxiety-like phenotype in OMetS females. The novel object recognition test showed that exclusively OMetS males had long-term memory impairment. In the reciprocal social interaction test, OMetS displayed a lower number of social interactions, with a notable increase in "socially inactive" behavior observed exclusively in females. Additionally, in the three-chamber test, social preference and social novelty indexes were found to be lower solely among OMetS females. An increase in visceral fat concomitantly with hypertriglyceridemia was the relevant postmortem metabolic finding in OMetS females. In summary, maternal MetS leads to enduring damage and adverse effects on offspring neurobehavior and metabolism, with notable sexual dimorphism.

A short-term rodent model for non-alcoholic steatohepatitis induced by a high-fat diet and carbon tetrachloride.

Several models of mice-fed high-fat diets have been used to trigger non-alcoholic steatohepatitis and some chemical substances, such as carbon tetrachloride. The present study aimed to evaluate the joint action of a high-fat diet and CCl4 in developing a short-term non-alcoholic steatohepatitis model. C57BL6/J mice were divided into two groups: standard diet-fed (SD), the high-fat diet-fed (HFD) and HFD + fructose-fed and carbon tetrachloride (HFD+CCl4). The animals fed with HFD+CCl4 presented increased lipid deposition compared with both SD and HFD mice. Plasma cholesterol was increased in animals from the HFD+CCl4 group compared with the SD and HFD groups, without significant differences between the SD and HFD groups. Plasma triglycerides showed no significant difference between the groups. The HFD+CCl4 animals had increased collagen deposition in the liver compared with both SD and HFD groups. Hydroxyproline was also increased in the HFD+CCl4 group. Liver enzymes, alanine aminotransferase and aspartate aminotransferase, were increased in the HFD+CCl4 group, compared with SD and HFD groups. Also, CCl4 was able to trigger an inflammatory process in the liver of HFD-fed animals by promoting an increase of ∼2 times in macrophage activity, ∼6 times in F4/80 gene expression, and pro-inflammatory cytokines (IL-1b and TNFa), in addition to an increase in inflammatory pathway protein phosphorylation (IKKbp). HFD e HFD+CCl4 animals increased glucose intolerance compared with SD mice, associated with reduced insulin-stimulated AKT activity in the liver. Therefore, our study has shown that short-term HFD feeding associated with fructose and CCl4 can trigger non-alcoholic steatohepatitis and cause damage to glucose metabolism.

The Impact of Excessive Fructose Intake on Adipose Tissue and the Development of Childhood Obesity.

Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.

Development of a tamarind-based functional beverage with partially-hydrolyzed agave syrup and the health effects of its consumption in C57BL/6 mice.

Excess consumption of sweetened beverages is associated with a global rise in metabolic diseases. Tamarind and partially-hydrolyzed agave syrup have potential for developing healthier beverages. Our objective was to develop a functional beverage using these ingredients (PH-AS-B). We also evaluate shelf-life stability (physicochemical, microbiological, and antioxidant properties) and health effects in C57BL/6 mice compared with tamarind beverages sweetened with glucose or fructose. Optimal tamarind extraction conditions were a 1:10 ratio (g pulp/mL water) and boiling for 30 min, and the resulting beverage had a shelf life of two months at 4 °C. Non-volatile metabolites were identified using HPLC/MS. PH-AS-B was associated with decreased blood cholesterol (5%) and triglyceride (20-35%) concentrations in healthy mice as well as lower lipid (82%) concentrations and evidence of protein oxidation (42%) in the liver, compared with glucose- and fructose-sweetened tamarind beverages. In conclusion, PH-AS-B was stable and associated with beneficial metabolic properties in healthy mice.

Physiological evaluation of yeast strains under anaerobic conditions using glucose, fructose, or sucrose as the carbon source.

The aim of this study was to evaluate the physiology of 13 yeast strains by assessing their kinetic parameters under anaerobic conditions. They included Saccharomyces cerevisiae CAT-1 and 12 isolated yeasts from different regions in Brazil. The study aimed to enhance understanding of the metabolism of these strains for more effective applications. Measurements included quantification of sugars, ethanol, glycerol, and organic acids. Various kinetic parameters were analyzed, such as specific substrate utilization rate (qS), maximum specific growth rate (µmax), doubling time, biomass yield, product yield, maximum cell concentration, ethanol productivity (PEth), biomass productivity, and CO2 concentration. S. cerevisiae CAT-1 exhibited the highest values in glucose for µmax (0.35 h-1), qS (3.06 h-1), and PEth (0.69 gEth L-1 h-1). Candida parapsilosis Recol 37 did not fully consume the substrate. In fructose, S. cerevisiae CAT-1 stood out with higher values for µmax (0.25 h-1), qS (2.24 h-1), and PEth (0.60 gEth L-1 h-1). Meyerozyma guilliermondii Recol 09 and C. parapsilosis Recol 37 had prolonged fermentation times and residual substrate. In sucrose, only S. cerevisiae CAT-1, S. cerevisiae BB9, and Pichia kudriavzevii Recol 39 consumed all the substrate, displaying higher PEth (0.72, 0.51, and 0.44 gEth L-1 h-1, respectively) compared to other carbon sources.

Ingestion of Bean Leaves Reduces Metabolic Complications and Restores Intestinal Integrity in C57BL/6 Mice with Obesity Induced by a High-Fat and High-Fructose Diet.

Consumption of foods with fiber and compounds can promote gastrointestinal health and reduce obesity complications. Therefore, treatment with common bean leaves (BL) against obesity was evaluated in mice with a high-fat and high-fructose diet (HFFD) for 14 weeks. The bromatological and phytochemical characterization of BL were determined. Afterwards, the animals were supplemented with BL (10%) or a standard diet (SD) as a strategy to encourage a healthy diet for 12 additional weeks. Changes in body composition, lipid profile, and intestinal integrity were analyzed. The characterization of BL stood out for its content of 27.2% dietary fiber, total phenolics (475.04 mg/100 g), and saponins (2.2 mg/100 g). The visceral adipose tissue (VAT) decreased in the BL group by 52% compared to the HFFD group. Additionally, triglyceride levels were 23% lower in the BL consumption group compared to the HFFD group. The improvement in lipid profile was attributed to the 1.77-fold higher fecal lipid excretion in the BL consumption group compared to the HFFD group and the inhibition of pancreatic lipase by 29%. Furthermore, BL supplementation reduced the serum levels of IL-6 (4.4-fold) and FITC-dextran by 50% compared with those in the HFFD group. Metabolic endotoxemia was inhibited after BL supplementation (-33%) compared to the HFFD group. BL consumption as a treatment in obese mice reduces adipose tissue accumulation and improves the lipid profile. Furthermore, we report for the first time that BL consumption improves intestinal integrity.

Differential consumption of malic acid and fructose in apple musts by Pichia kudriavzevii strains.

AIMS: To assess the capability of Pichia kudriavzevii strains isolated from wine, cider, and natural environments in North Patagonia to produce ciders with reduced malic acid levels. METHODS AND RESULTS: Fermentation kinetics and malic acid consumption were assessed in synthetic media and in regional acidic apple musts. All P. kudriavzevii strains degraded malic acid and grew in synthetic media with malic acid as the sole carbon source. Among these strains, those isolated from cider exhibited higher fermentative capacity, mainly due to increased fructose utilization; however, a low capacity to consume sucrose present in the must was also observed for all strains. The NPCC1651 cider strain stood out for its malic acid consumption ability in high-malic acid Granny Smith apple must. Additionally, this strain produced high levels of glycerol as well as acceptable levels of acetic acid. On the other hand, Saccharomyces cerevisiae ÑIF8 reference strain isolated from Patagonian wine completely consumed reducing sugars and sucrose and showed an important capacity for malic acid consumption in apple must fermentations. CONCLUSIONS: Pichia kudriavzevii NPCC1651 strain isolated from cider evidenced interesting features for the consumption of malic acid and fructose in ciders.

Production of polyhydroxybutyrate by coupled saccharification-fermentation of inulin.

Inulin is a fructose-based polysaccharide that can be found in several plant species, from grass and onions to chicory roots; thus, it has the potential to be an excellent renewable source of fructose for several industrial applications. Among them, inulin hydrolysis can be coupled to a fermentation operation to produce polyhydroxybutyrate (PHB) using Cupriavidus necator H16. This work reports the PHB production process involving chicory root inulin hydrolysis using inulinase Novozym 960 followed by a C. necator fermentation. It was found that the maximum saccharification (95% wt.) was reached at 269 U/ginulin after 90 min. The hydrolysates obtained were then inoculated with C. necator, leading to a biomass concentration of 4 g/L with 30% (w/w) polymer accumulation. Although PHB production was low, during the first hours, the cell growth and polymer accumulation detected did not coincide with a fructose concentration decrease, suggesting a simultaneous saccharification and fermentation process, potentially alleviating the product inhibition inherent to the inulinase-fructose system. The characterization of the obtained PHB showed a polymer with more homogeneous values of Mw, and better thermal stability than PHB produced using pure fructose as a fermentation substrate. The results obtained demonstrate a viable alternative carbon substrate for PHB production, opening the possibility for inulin-rich renewable feedstock valorization.

Maternal exercise during pregnancy modulates genotoxicity caused by high fructose consumption in mice offspring.

Pregnancy is a period that is characterized by several metabolic and physiological changes and requires special attention, especially with regard to the relationship between feeding and foetal development. Therefore, the objective of this study was to evaluate whether the practice of voluntary physical exercise (VPE) in combination with chronic consumption of fructose (FRU) from the beginning of life and/or until the gestational period causes genotoxic changes in pregnant females and in their offspring. Seventy Swiss female mice received FRU in the hydration bottle and/or practiced VPE for 8 weeks (prepregnancy/pregnancy). After the lactation period, the offspring groups were separated by sex. It was observed that the consumption of FRU affected the food consumption, serum concentration of FRU, and glycemic profile in the mothers and that the VPE decreases these parameters. In addition, FRU was genotoxic in the mothers' peripheral tissues and VPE had a preventive effect on these parameters. The offspring showed changes in food consumption, serum FRU concentration, and body weight, in addition to an increase in the adiposity index in male offspring in the FRU (FRU) group and a decrease in the FRU + VPE group. FRU leads to hepatic steatosis in the offspring and VPE was able to decrease the area of steatosis. In addition, FRU led to genotoxicity in the offspring and VPE was able to modulate this effect, reducing damages. In conclusion, we observed that all interventions with VPE had nutritional, genetic, and biochemical benefits of the mother and her offspring.

Swimming training and caffeine supplementation protects against metabolic syndrome-induced nuclear factor-κB activation and cognitive deficits in rats.

Metabolic syndrome (MS) is a disorder that increasingly affects the world population, mainly because of changes in lifestyle and dietary habits. In this regard, both physical exercise and caffeine are low-cost and easily accessible therapies that separately have shown positive effects against metabolic disorders. Therefore, we hypothesized that physical exercise combined with caffeine could have a synergistic effect in the treatment of MS, risk factors, and cognitive deficits. Animals were divided into 8 groups and received fructose (15% w/v) or vehicle for 10 weeks. Swimming training and caffeine (6 mg/kg) started 4 weeks after fructose administration. Trained animals presented decreased body weight and visceral fat mass and increased soleus weight compared with untrained fructose-treated animals. Caffeine supplementation also prevented the gain of visceral fat mass induced by fructose. Furthermore, both treatments reversed fructose-induced decrease in glucose clearance over time and fructose-induced increase in 4-hydroxynonenal and nuclear factor-κB immunoreactivity. Physical training also improved the lipidic profile in fructose-treated animals (high-density lipoprotein, low-density lipoprotein, and triglycerides), improved short-term, long-term, and localization memory, and reversed the fructose-induced deficit in short-term memory. Physical training also increased nuclear factor erythroid 2-related factor 2 immunoreactivity per se. Considering that physical training and caffeine reversed some of the damages induced by fructose it is plausible to consider these treatments as alternative, nonpharmacological, and low-cost therapies to help reduce MS-associated risk factors; however, combined treatments did not show additive effects as hypothesized.

Parental fructose consumption induces early baroreflex dysfunction in offspring: impact on arterial pressure and on insulin resistance.

Fructose overconsumption is a worldwide trend, and it has been found to cause metabolic disorders in parents and their offspring. Additionally, metabolic syndrome has been closely associated with increased cardiovascular risk. In this study, we hypothesized that the chronic fructose consumption by parents could trigger autonomic dysfunction and cardiometabolic disorders in their offspring. Wistar rats undergo an intake of 10% of fructose in drinking water or regular water for 60 days before mating. Their offspring, control (C) and fructose (F) groups, were evaluated 30 days after weaning. Lower birth weight, increased levels of blood triglycerides and insulin resistance were observed in F compared to C group. The offspring of the fructose parents showed increased mean arterial pressure (C: 104 ± 1 vs. F: 111 ± 2 mmHg) and baroreflex sensitivity impairment, characterized by reduced bradycardic (C: -1.6 ± 0.06 vs. F: -1.3 ± 0.06 bpm/mmHg) and tachycardic responses (C: -4.0 ± 0.1 vs. F: -3.1 ± 0.2 bpm/mmHg). Finally, a higher baroreflex-induced tachycardia was associated with lower insulin tolerance (r = -0.55, P < 0.03) and higher systolic arterial pressure (r = 0.54, P < 0.02). In conclusion, our findings indicate that the excessive consumption of fructose by parents is associated with early autonomic, cardiovascular, and metabolic derangement in the offspring, favoring an increased cardiometabolic risk when they reach adulthood.

Growth kinetics of Lactococcus lactis and Lactobacillus casei in liquid culture medium containing as prebiotics inulin or fructose.

BACKGROUND: Predictive microbiology is a tool that allows us to evaluate the behavior of the concentration of biomass and estimated cells under extrinsic conditions, providing scientific and industrial benefits. In the present study, the growth of L. lactis and L. casei combined with inulin and fructose was modeled using the Gompertz sigmoidal growth functions and plotted using data obtained from batch culture in relation to biomass and cell concentration expressed as estimates in ln N (OD600nm and cells mL-1 ) as a function of time. RESULTS: The results of the kinetic modeling indicated that (T1) A1B1 = L. lactis + fructose and (T4) A2B2 = L. casei + inulin presented the best function coefficients and best fits in most cases compared to the rest. The specific growth rate of the maximum acceleration was from 0.364 to 0.473 h-1 and 0.100 to 0.129 h-1 , the concentration of bacterial cells (A) was from 0.556 to 0.713 and 0.425 to 0.548 respectively and the time where (µ) occurred with a greater magnitude (L) fluctuated between 0.854 and 0.802 and when this time in (L) is very fast, it presents values of ≤0.072 to ≤0.092. Its coefficient of determination and/or multiple regression (R2 ) obtained in the two adjustments was 0.97. CONCLUSION: It was possible to predict the influence of the carbon source on the behavior of maximum growth rates, higher consumption due to nutrient affinity and shorter growth time. © 2023 Society of Chemical Industry.

Effect of Low-Dose Progesterone on Glycemic Metabolism, Morphology and Function of Adipose Tissue and Pancreatic Islets in Diet-Induced Obese Female Mice.

BACKGROUND: Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual's health by predisposing to several other diseases. About twice as many women as men suffer from severe obesity and, in fact, there are stages in a woman's life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes. METHODS: Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol. RESULTS: Animals fed a hypercaloric diet exhibited obesity with increased body weight (p < 0.0001), adipocyte hypertrophy (p < 0.0001), hyperglycemia (p = 0.03), and glucose intolerance (p = 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (p < 0.0001) and glucose-stimulated insulin secretion (p = 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (p = 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets. CONCLUSIONS: Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.

Long-term hepatic damage in high-fructose-fed C57BL/6 mice: hepatic fibrogenesis, endoplasmic reticulum stress markers, and fibrosis.

The rising fructose intake in sugar-sweetened beverages and ultra-processed foods relates to the high incidence of nonalcoholic fatty liver disease. This study aimed to examine the effects of long-term high-fructose diet intake (for 16 or 20 weeks) on progressive hepatic damage, focusing on the endoplasmic reticulum stress markers and fibrogenesis as possible triggers of liver fibrosis. Forty 3-month-old male C57BL/6J mice were randomly divided into four nutritional groups: C16 (control diet for 16 weeks), C20 (control diet for 20 weeks), HFRU16 (high-fructose diet for 16 weeks), and HFRU20 (high-fructose diet for 20 weeks). Both HFRU groups showed oral glucose intolerance and insulin resistance, but only the HFRU20 group exhibited increased inflammation. The increased lipogenic and endoplasmic reticulum stress markers triggered hepatic fibrogenesis. Hence, time-dependent perivascular fibrosis with positive immunostaining for alpha-smooth muscle actin and reelin in HFRU mice was observed, ensuring fibrosis development in this mouse model. Our study showed time-dependent and progressive damage on hepatic cytoarchitecture, with maximization of hepatic steatosis without overweight in HFRU20 mice. ER stress and liver inflammation could mediate hepatic stellate cell activation and fibrogenesis, emerging as targets to prevent NAFLD progression and fibrosis onset in this dietary model.