Tucker, Michelle Z., and Lorraine P. Turcotte. Brief food restriction increases FA oxidation and glycogen synthesis under insulin-stimulated conditions. Am J Physiol Regulatory Integrative Comp Physiol 282: R1210-R1218, 2002 10.1152/ajpregu.00248.2001.-To determine the effects of brief food restriction on fatty acid (FA) metabolism, hindlimbs of F344/BN rats fed either ad libitum (AL) or food restricted (FR) to 60% of baseline food intake for 28 days were perfused under hyperglycemic-hyperinsulinemic conditions (20 mM glucose, 1 mM palmitate, 1,000 U/ml insulin, [3-3 H]glucose, and [1-14 C]palmitate). Basal glucose and insulin levels were significantly lower (P Ͻ 0.05) in FR vs. AL rats. Palmitate uptake (34.3 Ϯ 2.7 vs. 24.5 Ϯ 3.1 nmol/g/min) and oxidation (3.8 Ϯ 0.2 vs. 2.7 Ϯ 0.3 nmol ⅐ g Ϫ1 ⅐ min Ϫ1 ) were significantly higher (P Ͻ 0.05) in FR vs. AL rats, respectively. Glucose uptake was increased in FR rats and was accompanied by significant increases in red and white gastrocnemius glycogen synthesis, indicating an improvement in insulin sensitivity. Although muscle triglyceride (TG) levels were not significantly different between groups, glucose uptake and total preperfusion TG concentration were negatively correlated (r 2 ϭ 0.27, P Ͻ 0.05). In conclusion, our results show that under hyperglycemic-hyperinsulinemic conditions, brief FR resulted in an increase in FA oxidative disposal that may contribute to the improvement in insulin sensitivity. food restriction; fatty acid uptake; intramuscular triglycerides; insulin sensitivity; skeletal muscle FOOD RESTRICTION (FR) has been shown to affect skeletal muscle carbohydrate metabolism by improving insulin sensitivity (7,8,25). Furthermore, improvements in insulin-stimulated glucose transport have been observed after only 5 days of FR (8). As suggested by the presence of an inverse relationship between insulin sensitivity and muscle triglyceride (TG) content (35), an inherent capacity of muscle to take up and dispose of a fatty acid (FA) load could be critical to the development of metabolic abnormalities associated with insulin resistance. Thus improvements observed in carbohydrate metabolism after FR may be linked to dietary-induced alterations in FA metabolism. Further support for a relationship between carbohydrate and FA metabolism with FR comes from a recent study by Man and coworkers (24). They observed that 4 mo of FR decreased TG levels by 50% in the soleus muscles of young adult Otsuka Long-Evans Tokushima Fatty rats (24). The decrease in TG was paralleled by significant improvements in insulin-stimulated glucose uptake measured during a euglycemic-hyperinsulinemic clamp (24). Thus it appears that alterations in FA metabolism with FR may affect insulin sensitivity in muscle.Alterations in muscle FA disposal could be due to changes in rates of FA uptake, oxidation, or storage by muscle. It has recently become evident that alterations in FA uptake could be of primary importance in the regulation of FA utilization in muscle (4,21,40). Indeed, evidence su...