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Objective: The aim of the study is to determine the response of muscle lipid peroxidation and the fatty-acid profile of three groups of mice-high body weight (DU6) obesity-prone mice, high treadmill performance (DUhTP) lean mice, and unselected control mice (DUK) fed high-fat diets (HFDs) rich in ω-3 or ω-6 polyunsaturated fatty acids (PUFA)., Methods: The isocaloric HFDs were enriched with either ω-3 PUFA (27% fish oil, ω-3 HFD) or ω-6 PUFA (27% sunflower oil, ω-6 HFD), and the control group was fed standard chow (7.2% fat). Statistical calculations were done with procedure GLM of SAS., Results: As expected, the ω-3 and ω-6 PUFA-rich HFDs showed significant effects on fatty-acid concentrations of skeletal muscle in all three lines of mice compared with the standard chow. The investigations of muscle lipid peroxidation revealed that the ω-3 PUFA-rich HFD caused the highest lipid peroxidation values in muscle of lean DUhTP mice and unselected control DUK mice. However, lower lipid peroxidation levels were observed in the obesity-prone DU6 mice. In contrast, the ω-6 PUFA-rich HFD did not influence lipid peroxidation in muscle of any of the different lines of mice. The present study suggests that a higher overall antioxidant capacity in the muscle tissue of obesity-prone DU6 mice may lead to lower levels of reactive oxygen species formation by ω-3 PUFA-rich HFDs in comparison with lean DUhTP mice., Conclusion: These studies raise the possibility that obesity per se may be protective against oxidative damage when high ω-3 PUFA diets are used., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Effective regulation of energy metabolism is vital for the maintenance of optimal health, and an inability to make these dynamic adjustments is a recognized cause of obesity and metabolic disorders. Epidemiological and experimental studies have highlighted the role of prenatal factors in the disease process, and it is now generally accepted that maternal nutrition during pregnancy significantly influences intrauterine development, shaping postnatal health. Consequences of impaired nutrition during fetal development include intrauterine growth restriction (IUGR) and subsequent obesity development in adult life. We have previously shown that prenatal undernutrition has a lasting effect on behavior, with IUGR offspring expressing a higher preference for voluntary exercise, and moderate daily exercise preventing obesity development. The present study investigated skeletal muscle structure in IUGR offspring and how moderate daily exercise drives changes in metabolic pathways that promote obesity prevention. Pregnant Wistar rats were either fed chow ad libitum or undernourished, generating control or IUGR offspring respectively. Although red muscle structure indicated higher oxidative capacity in IUGR offspring, obesity prevention was not due to increased fatty acid oxidation, indicated by decreased peroxisomal proliferator-activated receptor-gamma coactivator 1 and carnitine-palmitoyltransferase 1 expression. In contrast, increased protein kinase Czeta expression and glycogen content in white muscle of exercised IUGR offspring suggests an enhanced capacity for anaerobic utilization of glucose. Furthermore, exercise-induced lactate accumulation was effectively prevented by stimulation of a lactate shuttle, driven by the increases in monocarboxylate transporters-4 and -1 in white muscle. This enhanced metabolic flexibility in IUGR offspring may facilitate muscle contractile performance and therefore support moderate daily exercise for effective obesity prevention.

Obesity and its associated comorbidities are of major worldwide concern. It is now recognized that there are a number of metabolically distinct pathways of obesity development. The present paper investigates the effect of moderate daily exercise on the underlying mechanisms of one such pathway to obesity, through interrogation of metabolic flexibility. Pregnant Wistar rats were either fed chow ad libitum or undernourished throughout pregnancy, generating control or intrauterine growth restricted (IUGR) offspring, respectively. At 250 d of age, dual-emission x-ray absorptiometry scans and plasma analyses showed that moderate daily exercise, in the form of a measured amount of wheel running (56 m/d), prevented the development of obesity consistently observed in nonexercised IUGR offspring. Increased plasma C-peptide and hepatic atypical protein kinase Czeta levels explained increased glucose uptake and increased hepatic glycogen storage in IUGR offspring. Importantly, whereas circulating levels of retinol binding protein 4 were elevated in obese, nonexercised IUGR offspring, indicative of glucose sparing without exercise, retinol binding protein 4 levels were normalized in the exercised IUGR group. These data suggest that IUGR offspring have increased flexibility of energy storage and use and that moderate daily exercise prevents obesity development through activation of distinct pathways of energy use. Thus, despite a predisposition to develop obesity under sedentary conditions, obesity development was prevented in IUGR offspring when exercise was available. These results emphasize the importance of tailored lifestyle changes that activate distinct pathways of metabolic flexibility for obesity prevention.

High dietary energy and protein supply is common practice in livestock nutrition, aiming to maximize growth and production performance. However, a chronic nutritional surplus induces obesity, promotes insulin insensitivity, and triggers low-grade inflammation. Thirty Holstein bulls were randomly assigned to two groups, low energy and protein (LEP), and high energy and protein (HEP) intake, provided from the 13th to the 20th month of life. Body weight, carcass composition, laminitis score, and circulating insulin and glucose concentrations were assessed. The expression and extent of phosphorylation of insulin signaling proteins were measured in the liver, muscle, and adipose tissue. The sphingolipid metabolome was quantified by a targeted liquid chromatography-mass spectrometry based metabolomics approach. The HEP bulls were obese, had hyperinsulinemia with euglycemia, and expressed clinical signs of chronic laminitis. In the liver, protein kinase B (PKB) phosphorylation was decreased and this was associated with a higher tissue concentration of ceramide 16:0, a sphingolipid that diminishes insulin action by dephosphorylating PKB. In the adipose tissue, insulin receptor expression was lower in HEP bulls, associated with higher concentration of hexosylceramide, which reduces the abundance of functional insulin receptors. Our findings confirm that diet-induced metabolic inflammation triggers ceramide accumulation and disturbs insulin signaling. As insulin insensitivity exacerbates metabolic inflammation, this self-reinforcing cycle could explain the deterioration of metabolic health apparent as chronic laminitis. By demonstrating molecular relationships between insulin signaling and sphingolipid metabolism in three major tissues, our data extend our mechanistic understanding of the role of ceramides in diet-induced metabolic inflammation. [ABSTRACT FROM AUTHOR]

Metabolic flexibility is the body’s ability to adapt to changing energy demand and nutrient supply. Maternal undernutrition causes growth restriction at birth and subsequent obesity development. Intriguingly, metabolic flexibility is maintained due to adaptations of muscle tissue. The aim of the present study was to investigate developmental pathways of these adaptive changes. Wistar rats received standard chow at either ad libitum (AD) or 30% of ad libitum intake (UN) throughout pregnancy. At all ages, metabolic status indicated similar insulin sensitivity in AD and UN offspring despite the development of adiposity in UN offspring at weaning. Type IIA fiber size was reduced in soleus muscle of UN offspring at weaning and they had a higher percentage of type I fibers in adulthood with a concomitantly higher oxidative capacity. Plasticity of muscle was present during the postnatal period and proposes novel pathways for the dynamic development of metabolic flexibility throughout postnatal life. [ABSTRACT FROM AUTHOR]