Abstract

Aging is associated with increased visceral adiposity and a decrease in the amount of brown adipose tissue and muscle mass, known as sarcopenia, which results in the development of metabolic alterations such as insulin resistance. In this study, we aimed to analyze whether 3-week supplementation with a phenolic-rich olive leaf extract (OLE) to 24 months-old male Wistar rats orally (100 mg/kg) attenuated the aging-induced alterations in body composition and insulin resistance. OLE treatment increased brown adipose tissue and attenuated the aging-induced decrease in protein content and gastrocnemius weight. Treatment with OLE prevented the aging-induced increase in the expression of PPAR-γ in visceral and brown adipose tissues, while it significantly increased the expression of PPAR-α in the gastrocnemius of old rats and reduced various markers related to sarcopenia such as myostatin, HDAC-4, myogenin and MyoD. OLE supplementation increased insulin sensitivity in explants of gastrocnemius and epididymal visceral adipose tissue from aged rats through a greater activation of the PI3K/Akt pathway, probably through the attenuation of inflammation in both tissues. In conclusion, supplementation with OLE prevents the loss of muscle mass associated with aging and exerts anti-inflammatory and insulin-sensitizing effects on adipose tissue and skeletal muscle.

Highlights

  • Aging is associated with changes in body composition that are characterized by a significant decrease in muscle mass and an increase and redistribution of fat mass that is mainly concentrated in the central area of the body [1]

  • Sarcopenia associated with aging causes an increase in the expression of myostatin [10], a protein that inhibits the progression of the cell cycle and regulates the levels of factors that control muscle growth [11]

  • Aging did not modify the amount of interscapular brown adipose tissue, but it induced a significant increase in the relative weights of both epididymal and lumbar adipose tissues (p < 0.001 for both)

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Summary

Introduction

Aging is associated with changes in body composition that are characterized by a significant decrease in muscle mass and an increase and redistribution of fat mass that is mainly concentrated in the central area of the body [1]. These changes are related to functional decline and may predict mortality due, at least in part, to the increase in the waist circumference and waist-to-hip ratio, which is associated with an increased risk of developing cardiovascular diseases [2]. Myostatin negatively impacts muscle metabolism through inhibition of AMPK kinase and other effectors, which results in impaired mitochondrial biogenesis, insulin sensitivity and beta-oxidation, promoting the development of muscle lipotoxicity and apoptosis of muscle fibers [12]

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