l-Carnitine increases liver α-tocopherol and lowers liver and plasma triglycerides in aging ovariectomized rats

Abstract

The objective of this study was to determine whether dietary l-carnitine can influence the status of α-tocopherol, retinol and selected lipid parameters in aging ovariectomized rats, an animal model for the menopausal state. Fourteen Fisher-344 female rats 18 months old were acclimated for 4 weeks and ovarectomized. Seven rats per treatment were assigned to either a control group fed ad libitum AIN-93M diet or a carnitine group fed the same diet supplemented with l-carnitine. After an 8-week feeding period, blood and selected tissues were taken for analyses. No differences were noted in food intake, body weight, or organ weights due to l-carnitine. Dietary carnitine significantly increased liver α-tocopherol and tended to increase plasma α-tocopherol (P<.09). No changes in α-tocopherol were observed in other tissues including the brain, lungs and retroperitoneal fat. Retinol levels in plasma and tissues were not affected by supplemental l-carnitine. Significant decreases in liver and plasma triglyceride (TG) levels were noted, suggesting increased utilization of fatty acids. No differences were observed in the fatty acid profile of tissues. The results provide evidence that dietary supplementation of l-carnitine enhances the α-tocopherol status and improves the utilization of fat leading to lowering of the liver and plasma levels of TG in aging ovariectomized rats. Whether supplemental l-carnitine may be of benefit to postmenopausal women in lowering plasma TG and improving the antioxidant status remains to be studied.

Introduction

Menopause is a period in life associated with increased risk for heart disease, diabetes and other age related diseases [1], [2], [3]. Altered lipid metabolism contributes to the development of many of these diseases. The balance between lipid synthesis and breakdown pathways within a cell is, in part, controlled by the transfer of fatty acids across mitochondrial, peroxisomal and endoplasmic reticulum membranes. Fatty acids cross these membranes as acyl-carnitine derivatives to enter pathways for oxidation, acylation, chain shortening or chain elongation-desaturation [4]. Therefore, carnitine-dependent fatty acid transfer is central to lipid metabolism. During menopause, the body's ability to efficiently utilize nutrients begins to deteriorate, affecting carnitine status and subsequent lipid homeostasis. In this study, we used an aging ovariectomized rat model to simulate physiological changes associated with menopause to determine the effect of l-carnitine supplementation on tissue status of fat-soluble vitamins and profile of fatty acids.

l-Carnitine is a conditionally essential nutrient synthesized endogenously from lysine and methionine in the liver, kidney and brain [5], [6]. In the young healthy adult, the requirement for l-carnitine can be met by endogenous synthesis. However, with aging, tissue levels of carnitine decline in both humans and animals [7], [8], [9]. This adversely affects carnitine-dependent pathways. In aged rats, dietary carnitine stimulates the carnitine-dependent fatty acid transport system in the liver [10] and improves mitochondrial function and increased oxidative metabolism [11], whereas dietary carnitine has little effect on young animals. These observations suggest an increased need for dietary carnitine in the older rats. A decrease in capacity to oxidize fatty acids in the body due to less than optimal levels of carnitine could contribute to increased TG accumulation and storage in tissues. In addition, there is a growing body of evidence that the compromised status of fat-soluble vitamins including α-tocopherol and retinol may contribute to age-related diseases. A recent study with aged rats showed that carnitine supplementation improves the intestinal absorption of lipid and α-tocopherol [12]. At present, no information is available on whether supplemental carnitine improves the absorption and status of other fat-soluble vitamins in aging animals.

The brain, retina, liver and heart contain significant levels of docosahexaenoic acid (DHA, 22:6n-3) phospholipids, as required for their optimal function. DHA is synthesized from α-linolenic acid (18:3n-3) via a series of elongation and desaturation steps in the endoplasmic reticulum, followed by a chain-shortening step in the peroxisomes [13]. Carnitine has a role in the export of chain-shortened fatty acids from peroxisomes [14] and for transport of fatty acids across the endoplasmic reticulum [15]. If carnitine is limiting in tissues of aged animals, it is possible that carnitine supplementation may improve de novo synthesis of long-chain polyunsaturated fatty acids, particularly DHA, and alter the fatty acid profile of tissues.

The specific objectives of this study were to determine if dietary l-carnitine affects total body weight, accretion of lipid, vitamins A and E and tissue fatty acid profiles in aging ovariectomized rats. To our knowledge, this is the first report utilizing this animal model to study the effect of dietary carnitine.