Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions

Abstract

Tucker, Michelle Z., and Lorraine P. Turcotte. Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions. Am J Physiol Endocrinol Metab 282: E1102-E1109, 2002. First published January 8, 2002 10.1152/ajpendo.00175.2001The purpose of the present study was to examine the utilization of fatty acids (FA) and muscle substrates by skeletal muscle in young, middle-aged, and old adult rats under conditions of euglycemia with low insulin levels. Male Fischer 344 ϫ Brown Norway rats aged 5, 15, or 24 mo underwent hindlimb perfusion with a medium of 8 mM glucose, 1 mM palmitate, 25 U/ml insulin, [1-14 C]palmitate, and [3-3 H]glucose. Glucose and palmitate uptake were similar among age groups. The percent and total palmitate oxidized (nmol ⅐ min Ϫ1 ⅐ g Ϫ1 ) were 30-36 and 41-49% lower (P Ͻ 0.05) in 15-mo-and 24-mo-old than in 5-mo-old animals. Compared with 5-mo-and 15-mo-old animals, pre-and postperfusion muscle triglyceride (TG) levels were significantly (P Ͻ 0.05) elevated 91-305% in red and 118-219% in white muscles of 24-mo-old animals. Fatty acid-binding protein content was 40-64% higher (P Ͻ 0.05) in 24-mo-than in 5-mo-or 15-mo-old animals. In red muscle, hormone-sensitive lipase (HSL) content was 28% lower (P Ͻ 0.05) in 24-mo-than in 5-mo-old animals. These results indicate that, under euglycemic conditions in the presence of low insulin levels, the reduction in FA disposal to oxidation and the decrease in HSL content may contribute to the accumulation of TG in muscle of old animals. fatty acid metabolism; fatty acid-binding protein; Fischer 344 ϫ Brown Norway rats; glycogen; intramuscular triglycerides STUDIES ON THE EFFECTS OF AGING on fatty acid (FA) metabolism are scarce and in general indicate that cellular FA disposal is altered with aging (1, 8). In humans, aging has been shown to be associated with either a decrease (8) or an increase (4) in whole body FA oxidation at rest (8). When FA oxidation was blunted, the decrease could not be completely explained by a decrease in FA availability, because the rate of lipolysis has been shown to be higher in elderly subjects (9). This suggests that an age-related decline in FA oxidation would occur, in part, at the muscle level (8). These suggestions agree well with data collected in perfused working hearts showing that the rate of FA oxidation was lower in old than in young muscle (1). Furthermore, if cellular FA disposal to oxidation is decreased with aging, then this may be associated with an increase in muscle triglyceride (TG) levels. As suggested by the presence of an inverse relationship between insulin sensitivity and TG content in muscle (32), an alteration in the inherent capacity of the muscle to take up and dispose of a FA load could be critical to the development of metabolic abnormalities with aging. When it is considered that skeletal muscle can account for Ͼ50% of whole body FA disposal, it is critical to determine whether muscle FA oxidation per se is decreased with aging.Alterations in muscle FA disposal could also be due,...

Overexpression of Nmnat3 efficiently increases NAD and NGD levels and ameliorates age‐associated insulin resistance

“…Therefore, reduced ROS levels would likely be protective against diet‐induced and aging‐associated insulin resistance in Nmnat3 Tg mice. In accordance with the roles of NAD as a coenzyme in mitochondrial fatty acid oxidation, we observed the preferential use of fatty acids as an energy source in Nmnat3 Tg mice, and such shifts from carbohydrate‐ to fatty acid‐based energy production have been considered metabolically favorable during aging (Nguyen, Samson, Reddy, Gonzalez, & Sekhar, 2013; Schonfeld, Wieckowski, Lebiedzinska, & Wojtczak, 2010; Tucker & Turcotte, 2002). In addition, reduced capacity for fatty acid oxidation is related to insulin resistance (Kelley, Goodpaster, Wing, & Simoneau, 1999).…”

Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease

“…In older rats (15-24 mo vs. 5 mo), fatty acid oxidation was reduced while esterification was increased (441). The concurrent changes in fatty acid transporters were not detailed except to note that FABP pm expression was increased (441).…”

“…The concurrent changes in fatty acid transporters were not detailed except to note that FABP pm expression was increased (441). Similarly, in hearts of aged mice (52 wk), there is a twofold increase in intramyocardial lipid accumulation, as well as a ϳ50% reduction in fatty acid oxidation (254), which is accompanied by a dramatic increase in CD36 (4-fold) in these aged murine hearts compared with young hearts.…”

Crosstalk between mitochondrial (dys)function and mitochondrial abundance

“…Alternatively, mitochondrial turnover may also be reduced with age, resulting in an age-related accumulation of old, damaged, or non-functional mitochondria (Terman, 2006). Many studies show that fatty acid oxidation capacity is also decreased in a variety of tissues of elderly humans and older rodents (Melanson et al, 1997;Tucker and Turcotte, 2002;Park et al, 2006;Solomon et al, 2008). The expression of PGC-1a also declines with age in rodent skeletal muscle but such a decline can be blunted by CR Hepple et al, 2006).…”