Brief food restriction increases FA oxidation and glycogen synthesis under insulin-stimulated conditions

Abstract

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...

Metabolic profile and spontaneous physical activity modulation under short-term food restriction in young rats.

“…In periods of food restriction it was described a change from glycolytic to oxidative muscles 19 and it is known that the glucose uptake by the oxidative muscles increases during food restriction 25 , so, it is expected a decrease in serum glucose followed by decrease in the liver glycogen, as classically described to glycidic liver metabolism 26 . That glucose uptake by the oxidative muscles also leads to an increase in glycogen stores for heart and soleus, as found in our experiment.…”

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle

“…Enhanced gastrocnemius muscle mitochondrial gene expression is reported during chronic caloric restriction (47). Early increments of the ability for muscle substrate oxidative disposal also occur in the presence of acute or short-term reduction of nutrient intake (42,52). Expression of mitochondrial genes is in turn rapidly reduced in rodent muscle after 3 days of overfeeding and weight gain possibly associated with ghrelin suppression (37).…”

“…This hypothesis is also consistent with rapid changes in muscle lipid deposition after treatment with nutrient-sensing hormones insulin (2) and leptin (43) for 3-7 days in human and rodent models. It is therefore possible to hypothesize that early ghrelin increments (8,13) contribute to muscle metabolic adaptive changes in calorie-restricted states (47,52). Enhanced mitochondrial oxidative capacity could also have independently contributed to initiate or maintain ghrelin-induced triglyceride depletion in mixed gastrocnemius muscle, since reduced mitochondrial enzyme activities are related to impaired substrate utilization and muscle triglyceride accumulation in obese, type 2 diabetic, and aging individuals (21,25,39).…”

AMPKα2deficiency uncovers time dependency in the regulation of contraction-induced palmitate and glucose uptake in mouse muscle

“…Protein concentrations were determined with the Bradford protein assay (Bio-Rad, Hercules, CA). Muscle glycogen content was determined as glucose residues after hydrolysis of the muscle samples in 1 M HCl (100°C, 2 h) and corrected for free glucose in the sample (44). For ADP measurements, frozen GSP muscle samples (10 mg) were powdered under liquid N2 and homogenized as described above.…”