Acute Administration of Calafate (Berberis microphylla) Extract Induces the Expression of Thermogenic Markers and Modulates Gut Microbiota in Mice Fed a High-Fat Chow Diet.

INTRODUCTION: Obesity, characterized by excess adipose tissue, is a major public health problem worldwide. Brown adipose tissue (BAT) and beige adipose tissue participate in thermogenesis through uncoupling protein 1 (UCP1). Polyphenols including those from Calafate (a native polyphenol-rich Patagonian berry), are considered as potential anti-obesity compounds due to their pro-thermogenic characteristics. However, polyphenols are mainly metabolized by the gut microbiota (GM) that may influence their bioactivity and bioavailability. The aim of this study was to determine the impact of dietary administration with a Calafate polyphenol-rich extract on thermogenic activity of BAT and beige adipose tissue and GM composition. METHODS: Eight-week-old C57BL6 mice (n = 30) were divided into 4 groups to receive for 24 weeks a control diet (C), a high-fat diet alone (HF), or high-fat diet supplemented with Calafate extract (HFC) or the same high-fat diet supplemented with Calafate extract but treated with antibiotics (HFCAB) from week 19-20. Administration with Calafate extract (50 mg/kg per day) was carried out for 3 weeks from week 21-23 in the HFC and HFCAB groups. After euthanasia, gene expression of thermogenic markers was analyzed in BAT and inguinal white adipose tissue (iWAT). Transmission electron microscopy was performed to assess mitochondrial morphology and cristae density in BAT. GM diversity and composition were characterized by deep sequencing with the MiSeq Illumina platform. RESULTS: Calafate extract administration had no effect on weight gain in mice fed a high-fat diet. However, it prevented alterations in mitochondrial cristae induced by HFD and increased Dio2 expression in BAT and iWAT. The intervention also influenced the GM composition, preventing changes in specific bacterial taxa induced by the high-fat diet. However, the antibiotic treatment prevented in part these effects, suggesting the implications of GM. CONCLUSION: These results suggest that the acute administration of a Calafate extract modulates the expression of thermogenic markers, prevents alterations in mitochondrial cristae and intestinal microbiota in preclinical models. The study highlights the complex interaction between polyphenols, thermogenesis, and the GM, providing valuable insights into their potential roles in the treatment of obesity-related metabolic diseases.

El consumo de un extracto de calafate (Berberis microphylla) modifica marcadores de respuesta inmune en ratones delgados y obesos

RESUMEN La obesidad ha sido identificada como factor de riesgo de severidad de infecciones respiratorias. Apoyar la respuesta inmune en sujetos obesos es de interés. El presente trabajo evaluó el efecto del consumo de un extracto de calafate sobre marcadores de respuesta inmune en ratones delgados y obesos. Ratones C57BL/6J machos fueron expuestos por 82 días a dieta estándar (DE) y alta en grasas (DAG). A un subgrupo de ambos grupos, se les administró 50 y 100 mg [polifenoles totales]/kg peso de animal/día, de extracto, en las últimas dos semanas. Se evaluó expresión génica y secreción de marcadores de respuesta inmune, en tejido pulmonar y plasma. Se observó un efecto del tratamiento con extracto en la expresión de IFN-ϓ. Se observaron efectos inducidos por la DAG y el tratamiento con extracto de manera independiente, en la expresión de IL-12. Se observó un efecto global de la DAG sobre IFN-ϓ plasmático, específicamente una disminución en animales alimentados con DAG. Se observó una interacción entre la dieta y el tratamiento con extracto sobre IL-12 plasmática. El tratamiento utilizado modula marcadores que activan la respuesta inmune ante infecciones respiratorias principalmente de origen viral, en animales delgados y obesos.

ABSTRACT Obesity has been identified as a risk factor for severity of respiratory infections. Thus, the support of the immune response in obese subjects is of interest. The present work evaluated the effect of the consumption of a calafate extract on markers of the immune response in lean and obese mice. Male C57BL/6J mice were exposed for 82 days to a standard or a high-fat diet (HFD). A subgroup of both groups was given 50 and 100 mg [total polyphenols]/kg body weight/day of extract in the last two weeks. Gene expression and secretion of immune response markers were evaluated in lung tissue and plasma. An effect of extract treatment on IFN-ϓ expression was observed. Effects induced by the HFD and treatment with extract were observed independent of the expression of IL-12. An overall effect of the HF diet on plasma IFN-ϓ was observed, specifically a decrease in animals fed the HFD. An interaction between diet and extract treatment was observed over plasma IL-12. The treatment used modulates markers that activate the immune response to respiratory infections, mainly of viral origin, in lean and obese animals.

Caracterización de extractos de piel y hojas de Persea americana Mill. y analisis in vitro de sus potenciales propiedades anti-inflamatorias / Characterization of Persea americana Mill. peels and leaves extracts and analysis of its potential in vitro anti-inflammatory properties

Existe una tendencia mundial de incremento en prevalencia de enfermedades no transmisibles, que se caracterizan por un estado pro-inflamatorio crónico. Por lo tanto, es importante estudiar la relación entre alimentos y salud. La palta (Persea americana), sobresale en la industria por su valor nutricional. El procesamiento de la palta genera gran cantidad de subproductos, que contienen bioactivos con propiedades beneficiosas, como polifenoles. El objetivo del presente trabajo fue caracterizar cuatro extractos de palto (acuoso e hidroalcohólico; de hoja y de cáscara) y analizar sus posibles propiedades anti-inflamatorias in vitro. Fueron determinados polifenoles totales (con el método de Folin­Ciocalteau) y capacidad antioxidante (por FRAP y DPPH) de los extractos. Las propiedades anti-inflamatorias de los extractos fueron determinadas por la liberación de NO y de TNF-, y por la expresión génica de TNF-. Los resultados indican que los extractos hidroalcohólicos presentan más polifenoles (p<0,001) y capacidad antioxidante (p<0,001, por FRAP) que los acuosos. Mas aún, observamos que los extractos hidroalcohólicos de hojas presentaron mayores efectos anti-inflamatorios in vitro, especialmente el hidroalcohólico de hoja en liberación de NO (p<0,001, frente a tratamiento con LPS), acuosos e hidroalcohólicos en liberación de TNF- (p<0,05), y solo los hidroalcohólicos en la expresión de TNF- (p<0,01). En conclusión, los extractos hidroalcohólicos de palto, y especialmente el de hoja, presentan propiedades anti-inflamatorias in vitro que pueden ser consideradas para aplicaciones en mejoría de salud humana.

There is a worldwide trend of increasing prevalence of non-communicable diseases characterized by a chronic inflammatory state. Therefore, it is important to study the relationship between food and health. Avocado (Persea americana) stands out in food industry for its nutritional value. Industrials process of avocado generates a large number of by-products, which contain phytochemical compounds with antioxidant properties, such as polyphenols. The objective of the present research was to characterize four aqueous and hydroalcoholic extracts from avocado leaves and peels and analyze it possible anti-inflammatory properties in vitro. Total polyphenol content (with the Folin-Ciocalteau method) and antioxidant capacity (by FRAP and DPPH) were determined. Extracts inflammatory features were measured by NO and TNF- release, and by TNF- gene expression. Our results indicated that hydroalcoholic extracts present higher total polyphenol content (p<0.001) and antioxidant capacity (p<0.001, by FRAP) than the aqueous ones. Furthermore, we report that hydroalcoholic leaves extract presented greater in vitro anti-inflammatory effect, especially the leave hydroalcoholic regarding NO release (p<0.001, against LPS treatment), aqueous and hydroalcoholics regarding TNF- release (p<0.05), and only the hydroalcoholic in the TNF- gene expression (p<0.01). In conclusion, the avocado hydroalcoholic extracts, and especially from leaves, present in vitro anti-inflammatory features that might be considered for human health improvement applications.