Daily Consumption of Golden Berry (Physalis peruviana) Has Been Shown to Halt the Progression of Insulin Resistance and Obesity in Obese Rats with Metabolic Syndrome.

In a study addressing the high risk of chronic diseases in people with diabetes and obesity linked to metabolic syndrome, the impact of a Golden Berry diet was investigated using a diabetic animal model. Obese rats with diabetic characteristics were fed a diet containing five percent Golden Berry for 16 days. This study focused on various parameters including organ weights, expression of metabolic genes, and urinary biomarkers. Post-Golden Berry intake, there was a notable decrease in the body, liver, pancreas, visceral, and subcutaneous adipose tissue weights in these obese, hyperglycemic rats. In contrast, an increase in brown adipose tissue (BAT) cell mass was observed. This diet also resulted in reduced blood glucose levels and normalized plasma biochemical profiles, including cholesterol, triglycerides, LDL, and HDL levels. Additionally, it modulated specific urinary biomarkers, particularly pipe-colic acid, a primary marker for type 2 diabetes. Bioinformatics analysis linked these dietary effects to improved insulin signaling and adipogenesis. Regular consumption of Golden Berry effectively prevented insulin resistance and obesity in rats, underscoring its significant health benefits and the protective role of an antioxidant-rich diet against metabolic syndrome. These findings offer promising insights for future therapeutic strategies to manage and prevent obesity and related chronic diseases.

Main urinary biomarkers of golden berries (Physalis peruviana) following acute and short-term nutritional intervention in healthy human volunteers.

The metabolites entering the bloodstream and being excreted in urine as a result of consuming golden berries are currently unidentified. However, these metabolites potentially underlie the health benefits observed in various in vitro, animal, and human models. A nutritional intervention with 18 healthy human volunteers was performed, and urine was collected at baseline and after acute and short-term fruit consumption for 19 days. After UPLC-ESI/QToF-MS analysis, untargeted metabolomics was performed on the urine samples, and from the 50 most discriminant ions (VIP > 2) generated by a validated PLS-DA model (CV-ANOVA = 3.7e-35; R^2Y = 0.86, Q^2Y = 0.62 and no overfitting), 22 compounds were identified with relatively high confidence. The most discriminant metabolites confirmed by DHS/GC-MS2 analysis of volatiles in urine were sesquiterpenes (C15H22): 3 stereoisomers, ß-vatirenene, ß-vetivenene, and ß-vetispirene, and 2 isomers, eremophila-1(10),8,11-triene and α-curcumene. Another major urinary biomarker was 4ß-hydroxywithanolide E and its phase II derivatives, which were observed in urine for all individual up to 24 h after the fruit was consumed; thus, the bioavailability of this biomarker in humans was demonstrated for the first time. Additionally, the excretion of certain acylcarnitines and hypoxanthine in urine increased after golden berry consumption, which may be associated with a detoxifying effect and may occur because fats were utilized rather than carbohydrates to meet the body's energy needs. The main biomarkers of golden berry consumption are specific to this fruit, confirming its potential for the functional food market.

Hipertrofia y resistencia a la insulina en un modelo in vitro de obesidad y DMT2 inducida por alta glucosa e insulina / Hypertrophy and insulin resistance in an in vitro model of obesity and T2DM induced by high glucose and insulin

Resumen Introducción: La obesidad es considerada un factor de riesgo para desarrollar resistencia a la insulina. La expansión del tejido adiposo se ha relacionado con el aumento de la producción de citoquinas proinflamatorias que, junto a los ácidos grasos son responsables, al menos en parte, del desarrollo de la resistencia a la insulina y esta a su vez, facilita el desarrollo de diabetes mellitus tipo 2 (DMT2). Objetivo: El propósito de este estudio fue realizar y caracterizar un modelo in vitro de obesidad empleando concentraciones altas de glucosa e insulina en una línea de células adipocitarias. Métodos: Se indujo modelo de hipertrofia celular realizando un estímulo en adipocitos maduros con una concentración de glucosa (450 mg/dL) e insulina (106 pmol/L) (modelo HGHI). Tras estímulo se realizaron ensayos de viabilidad celular, diámetro celular, movilización de lípidos y marcadores de señalización de insulina. Resultados: Tras el tratamiento con HGHI, se evidencia hipertrofia adipocitaria, incremento en la acumulación de lípidos, reducción de la ruptura de éstos, alteración de la señalización de insulina y tendencia a modificación de proteínas de marcadores de estrés de retículo y estrés oxidativo. Conclusión: Estos resultados demuestran la validez del modelo in vitro que simula al menos en parte la obesidad asociada a insulino resistencia, siendo una herramienta útil para estudiar los mecanismos de susceptibilidad a obesidad y resistencia a la insulina inducida in vitro con diferentes moléculas.

Abstract Introduction: Obesity is considered a risk factor for developing insulin resistance. The increase in adipose tissue has been related to the increase in the production of pro-inflammatory cytokines, which together with fatty acids are responsible, at least in part, for the development of insulin resistance, and this in turn facilitates the development of T2 diabetes mellitus type 2 (DMT2). Objective: The purpose of this study was to perform and characterize an in vitro model of obesity using high concentrations of glucose and insulin on an adipocyte cell line. Methods: A cell hypertrophy model was induced by stimulating mature adipocytes with a concentration of glucose (450 mg/dL) and insulin (106 pmol/L) (HGHI model). The cell viability, cell diameter, lipid mobilization and insulin signalling markers were evaluated. Results: After HGHI treatment, adipocytes show hypertrophy, increase in lipid accumulation, reduction of lipid breakdown, alteration of insulin signalling, a tendency to modify proteins of reticulum stress markers and, oxidative stress. Conclusion: These results demonstrate a new in vitro model that simulates, at least in part, obesity associated with insulin resistance being a useful tool to study the mechanisms of susceptibility to obesity and insulin resistance induced in vitro by different molecules.

Plasma Metabolome Profiling by High-Performance Chemical Isotope-Labelling LC-MS after Acute and Medium-Term Intervention with Golden Berry Fruit (Physalis peruviana L.), Confirming Its Impact on Insulin-Associated Signaling Pathways.

PURPOSE: Golden berry (Physalis peruviana L.) is an exotic fruit exported from Colombia to different countries around the world. A review of the literature tends to demonstrate a hypoglycaemic effect with an improvement in insulin sensitivity after oral ingestion of fruit extracts in animal models. However, little is known about their potential effects in humans, and very little is known about the mechanisms involved. This study aimed at identifying discriminant metabolites after acute and chronic intake of golden berry. METHOD: An untargeted metabolomics strategy using high-performance chemical isotope-labelling LC-MS was applied. The blood samples of eighteen healthy adults were analysed at baseline, at 6 h after the intake of 250 g of golden berry (acute intervention), and after 19 days of daily consumption of 150 g (medium-term intervention). RESULTS: Forty-nine and 36 discriminant metabolites were identified with high confidence, respectively, after the acute and medium-term interventions. Taking into account up- and downregulated metabolites, three biological networks mainly involving insulin, epidermal growth factor receptor (EGFR), and the phosphatidylinositol 3-kinase pathway (PI3K/Akt/mTOR) were identified. CONCLUSIONS: The biological intracellular networks identified are highly interconnected with the insulin signalling pathway, showing that berry intake may be associated with insulin signalling, which could reduce some risk factors related to metabolic syndrome. Primary registry of WHO.

Effects of oleic (18: 1n-9) and palmitic (16: 0) fatty acids on the metabolic state of adipocytes / Efectos de los ácidos grasos oleico (18: 1n-9) y palmítico (16: 0) en el estado metabólico del adipocito

Abstract Background: Elevated serum-free fatty acid (FFA) levels induce insulin resistance (IR) or a protective mechanism to IR development in humans; it depends on FFA type. Objetive: This study explores the effects of oleic (OLA - unsatured) and palmitic (PAM - saturated) fatty acids on insulin action in mature adipocytes effect. Methods: Cells were incubated 18 h with or without OLA and PAM at 250 μM, and 500 μM. After the culture period, were measured: adipocyte viability, size, fatty acids mobilisation, insulin signalling proteins, and glucose uptake. Results: Adipocytes exhibited optimal viability tolerances regardless of the kinds of fatty acids used for treatment. However, adipocytes were hypertrophic after OLA and PAM stimuli. Additionally, lipogenesis (lipid synthesis), and lipolysis (lipid breakdown) were significantly increased by treatment with OLA, or PAM (500 μM) compared to control. Moreover, OLA results showed that there was no significant reduction in signalling cascades, except for a downstream proinflammatory response. Instead, PAM hypertrophic adipocytes were insulin resistant with alteration of proinflammatory and stress markers. Conclusions: Current findings suggest that PAM induces insulin resistance, mitochondrial and reticulum stress on fat cells compared to those treated with OLA that, protects adipocytes to all those alterations.

Resumen Introducción: Los niveles elevados de ácidos grasos libres (AGL) en suero inducen resistencia a insulina (RI) o un mecanismo de protección del desarrollo de RI en humanos, esto depende del tipo de AGL. Objetivo: Este estudio explora los efectos de los ácidos grasos oleico (insaturados - OLA) y palmítico (saturados - PAM) sobre la insulina en adipocitos maduros. Métodos: Las células se incubaron 18 h con o sin OLA y PAM a 250 μM y 500 μM. Después del período de cultivo, se evaluó en adipocitos: viabilidad, tamaño, movilización de ácidos grasos, proteínas de señalización de insulina y absorción de glucosa. Resultados: Los adipocitos mostraron viabilidad óptima independientemente de los tipos de ácidos grasos utilizados en el tratamiento. Los adipocitos eran hipertróficos tras estimulo con OLA y PAM. La lipogénesis (síntesis de lípidos) y la lipólisis (degradación de lípidos) aumentaron significativamente con el tratamiento con OLA o PAM (500 μM) en comparación con el control. En los resultados de OLA no se evidenció una reducción significativa en las cascadas de señalización de insulina, a excepción de una respuesta proinflamatoria posterior. En cambio, los adipocitos hipertróficos tratados con PAM presentaron resistencia a la insulina y alteración de los marcadores proinflamatorios y de estrés. Conclusiones: Nuestros hallazgos sugieren que PAM induce resistencia a la insulina, estrés mitocondrial y del retículo en las células grasas en comparación con aquellos tratados con OLA, AGL que, en cambio, protegen a los adipocitos de todas esas alteraciones.