# High-Fat Diet Anticipates Age-Related Sarcopenia Through Increased Oxidative Stress and Inflammation

## TL;DR

A high-fat diet speeds up age-related muscle loss by increasing oxidative stress and inflammation, worsening mitochondrial function.

## Contribution

The study shows how a high-fat diet accelerates sarcopenia by disrupting mitochondrial function and antioxidant defenses.

## Key findings

- High-fat diet increases oxidative stress and inflammation, worsening age-related metabolic and inflammatory changes.
- Antioxidant defenses fail in high-fat diet groups, leading to mitochondrial dysfunction.
- Reduced physical activity in high-fat diet rats may contribute to impaired mitochondrial function in skeletal muscle.

## Abstract

Ageing, a physiological process, and obesity, a pathological condition, are both associated with several metabolic alterations including energy imbalance, altered body composition, chronic low-grade inflammation, lipotoxicity, glucotoxicity, insulin resistance and mitochondrial dysfunctions. During ageing mitochondrial capacity declines and oxidative stress increases. However, the biphasic model of age-associated mitochondrial functions indicates that, before the ageing-associated decrease in mitochondrial respiration, this parameter increases in the transition from young adult to middle-aged, with a concomitant mild increase in ROS production that stimulates an antioxidant response, limiting the ageing-associated damages. Ageing-associated body composition changes can lead to sarcopenia, one of the most debilitating dysfunctions in the elderly. The sarcopenia is a known geriatric syndrome characterized by the loss of muscle mass and strength and mitochondria dysfunctions. These alterations of the disease can be exacerbated by obesity. Here, in an experimental animal model of diet-induced obesity, we evaluated the time-course changes in body composition, inflammatory and oxidative stress parameters, mitochondrial functions and antioxidant responses.

Male Wistar rats at 60 days of age were divided into two experimental groups: the first group received a standard diet; the second group received a high-fat diet (HFD). The animals from both groups were fed with the appropriate diet for 1, 3, 6, 12, or 24 weeks (n = 6 for each group and time point). At each time point, the animals were sacrificed and dissected to obtain the organs and tissues needed for analysis.

Our results clearly showed the contribution of high-fat diet in anticipating and worsening the metabolic and inflammatory alterations associated with age, in particular, highlighting the role of mitochondria in attempting the regulation of physiological alterations typical of aging.

In the HFD group the antioxidant defences fail their job because of the additional inflammation and oxidative stress due to the diet. HFD is related to decreased animals’ activity. Thus, cannot be excluded that the reduced physical activity may contribute, at least in part, to the impaired mitochondrial functions in the skeletal muscle of HFD rats. Altogether, our results clearly highlighted the contribution of HFD in anticipating and worsening the metabolic and inflammatory alterations associated with aging, including sarcopenia.

In the transition from youth to adult of healthy individuals, the physiological increase of mitochondrial activity paralleles to a mild increase in ROS production that stimulates the antioxidant response limiting the aging-associated damages. Obesity leads to mitochondrial dysfunction and oxidative stress, anticipating and worsening the metabolic and inflammatory alterations associated with age.Infographic compares physiological and obese conditions across young, adult, and middle-age stages using graphics of a running person and an obese figure. Physiological sequence shows healthy young mitochondria progressing to mild reactive oxygen species (ROS) increase in adulthood and mitochondrial decline in middle age. Obese sequence shows early mitochondrial damage in youth, leading to increased body lipid, ROS, and inflammatory markers, decreased antioxidant defense and body protein, and severe mitochondrial dysfunction by middle age.

In the transition from youth to adult of healthy individuals, the physiological increase of mitochondrial activity paralleles to a mild increase in ROS production that stimulates the antioxidant response limiting the aging-associated damages. Obesity leads to mitochondrial dysfunction and oxidative stress, anticipating and worsening the metabolic and inflammatory alterations associated with age.