PipeNig®-FL, a Fluid Extract of Black Pepper (Piper Nigrum L.) with a High Standardized Content of Trans-β-Caryophyllene, Reduces Lipid Accumulation in 3T3-L1 Preadipocytes and Improves Glucose Uptake in C2C12 Myotubes.

Federica Geddo,Rosaria Scandiffio,Giulia Querio,Massimo E Maffei,Erika Cottone,Susanna Antoniotti,Maria Pia Gallo,Patrizia Bovolin

doi:10.3390/nu11112788

Federica Geddo, Rosaria Scandiffio + Show 6 more

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https://doi.org/10.3390/nu11112788

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Abstract

Trans-β-caryophyllene (BCP) is a natural sesquiterpene hydrocarbon with several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, and cardioprotective functions. These properties are mainly due to its selective interaction with the peripherally expressed cannabinoid receptor 2. In addition, BCP activates peroxisome proliferated activator receptors α and γ and inhibits the Toll-like receptor signaling pathway. Given the growing scientific interest in BCP, the aim of our study was to investigate the metabolic effects of a black pepper extract (PipeNig®-FL), containing a high standardized content of BCP. In particular our interest was focused on its potential activity on lipid accumulation and glucose uptake. The extract PipeNig®-FL was chemically characterized by gas chromatography–mass spectrometry (GC–MS) and gas chromatography with flame-ionization detection (GC–FID), confirming a high content (814 mg/g) of BCP. Experiments were performed on 3T3-L1 preadipocytes and on C2C12 myotubes. Lipid content following 3T3-L1 adipogenic differentiation was quantified with AdipoRed fluorescence staining. Glucose uptake and GLUT4 membrane translocation were studied in C2C12 myotubes with the fluorescent glucose analog 2-NBDG and by immunofluorescence analysis. Here we show that PipeNig®-FL reduces 3T3-L1 adipocyte differentiation and lipid accumulation. Moreover, acute exposure of C2C12 myotubes to PipeNig®-FL improves glucose uptake activity and GLUT4 migration. Taken together, these results reveal interesting and novel properties of BCP, suggesting potential applications in the prevention of lipid accumulation and in the improvement of glucose uptake.

Highlights

Metabolic syndrome is a non-communicable disease characterized by visceral adiposity, insulin resistance, hyperlipidemia, hypertension and a chronic low-grade inflammatory state, often dragging into the onset of type 2 diabetes, coronary disease, stroke, and other disabilities
The multiple biological mechanisms included in metabolic syndrome provide a complex interorgan communication, involving adipokines, macrophages, endoplasmic reticulum stress, thyroid hormones, beta adrenergic hormones, gut microbiome and other factors, where epigenetic drivers represent the major component with respect to genetic predisposition [1]
The chemical composition of PipeNig® -FL was assessed by gas chromatography–mass spectrometry (GC–MS) and quantified by gas chromatography with flame-ionization detection (GC–FID), as specified in the Materials and Methods section

Summary

Introduction

Metabolic syndrome is a non-communicable disease characterized by visceral adiposity, insulin resistance, hyperlipidemia, hypertension and a chronic low-grade inflammatory state, often dragging into the onset of type 2 diabetes, coronary disease, stroke, and other disabilities. The pharmacological treatment of metabolic syndrome commonly involves anti-obesity drugs, thiazolidinediones (TZDs), metformin, statins, fibrates and several other drugs [2], but its management lies in the adoption of a healthy lifestyle [3]. Among active compounds naturally present in Piper nigrum, the dietary cannabinoid trans-β-caryophyllene (BCP) could be considered as a possible key component in the treatment of obesity and type 2 diabetes in the metabolic syndrome scenario [6]

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