The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice

Abstract

The Membrane Theory of Aging proposes that lifespan is inversely related to the level of unsaturation in membrane phospholipids. Calorie restriction (CR) without malnutrition extends lifespan in many model organisms, which may be related to alterations in membrane phospholipids fatty acids. During the last few years our research focused on studying how altering the predominant fat source affects the outcome of CR in mice. We have established four dietary groups: one control group fed 95% of a pre-determined ad libitum intake (in order to prevent obesity), and three CR groups fed 40% less than ad libitum intake. Lipid source for the control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or lard (high in saturated and monounsaturated fatty acids). Dietary intervention periods ranged from 1 to 18 months. We performed a longitudinal lifespan study and a cross-sectional study set up to evaluate several mitochondrial parameters which included fatty acid composition, H+ leak, activities of electron transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal muscle. These approaches applied to different cohorts of mice have independently indicated that lard as a fat source often maximizes the effects of 40% CR on mice. These effects could be due to significant increases of monounsaturated fatty acids levels, in accordance with the Membrane Theory of Aging.

Insulin Access to Skeletal Muscle is Preserved in Obesity Induced by Polyunsaturated Diet

“…Hyperinsulinemic compensation has been hypothesized to be a normal response to insulin resistance . Hyperinsulinemia can be driven by changes in insulin secretion and/or insulin clearance .…”

“…In skeletal muscle, mitochondria can adapt to a saturated fat diet by reducing proton leak, whereas proton leak is increased with diets high in omega-3 PUFAs (26), resulting in differential effects of these dietary fats on energy conservation and expenditure. In addition, there are distinct effects of dietary fat on mitochondrial enzyme activity, fission proteins, and apoptotic signaling (26); however, we did not investigate these mechanisms of insulin resistance in the current study.…”

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

“…Nevertheless, we have previously shown that mitochondrial phospholipid fatty acid composition was altered in liver and skeletal muscle from CR mice in a manner that reflected the unsaturated fatty acid composition of the diet with the consequent increase of n‐3 and n‐6 fatty acids in CRF‐ and CRS‐fed animals, respectively, and probably changing several properties of the membranes (Chen et al ., 2012, 2013). On the other hand, CRL‐fed animals showed a significantly higher proportion of mitochondrial monounsaturated fatty acids (especially oleic acid), a result that was accompanied by improved mitochondrial functions and ultrastructure (see Villalba et al ., 2015 for a recent review). Thus, it is very likely that an increase in monounsaturated fatty acids such as oleic acid may be involved in the beneficial effect of lard as a dietary fat in CR‐fed animals.…”

Effect of high-fat mixed lipid diet and swimming on fibre types in skeletal muscles of rats with colon tumours

“…In healthy rats, it was demonstrated that dietary lipids alter the fatty acid (FA) profile of mitochondrial membrane in multiple tissues, including skeletal muscle, which may elicit short- or long-term changes in reactive oxygen species (ROS) production by muscle mitochondria in muscle-specific manner. 26 , 27 Namely, 8 weeks of diet with 15% fat derived from soybean oil (n-6 PUFA-rich) or coconut oil (saturated FA-rich) resulted in changed activities of some antioxidant enzymes in muscle-specific manner. 27 Interestingly, despite the diverse activity of ROS scavenging enzymes found in SOL and white gastrocnemius muscles after both high fat diets, an increased lipid peroxidation was found in both muscles.…”