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Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up‐regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight‐week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin‐induced diabetes. Induction of diabetes increased DNA‐binding activity of heat shock factor‐1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL‐6 and TNF‐alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non‐diabetic rats. On the other hand, exercise training appeared to reverse the diabetes‐induced histological changes together with decreased expression of TGF‐beta as a key inducer of glomerulosclerosis, and decreased levels of IL‐6 and TNF‐alpha. Notably, HSP72 and TGF‐beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up‐regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers. [ABSTRACT FROM AUTHOR]

Summary: Background: Irisin has been suggested to protect against overweight. There are no previous data on the association of plasma fatty acid (FA) composition with plasma irisin. Objectives: We studied the association of FA composition with plasma irisin in normal weight and overweight/obese children. Methods: This cross‐sectional study included pre‐pubertal children (388 normal weight children and 55 overweight/obese children); 6–9 years of age, taking part in the Physical Activity and Nutrition in Children Study. After an overnight fast, we measured plasma FA composition by gas chromatography and plasma irisin levels by enzyme‐linked immunosorbent assay. Results: Higher proportion of total monounsaturated fatty acids in plasma cholesteryl esters (CEs) (β = 0.139, P = 0.003) and phospholipids (PLs) (β = 0.147, P = 0.002) and lower proportion of total polyunsaturated fatty acids in plasma CE (β = −0.130, P = 0.006) and PL (β = −0.165, P < 0.001) were associated with higher plasma irisin level in the whole study group. The association of plasma FA composition with plasma irisin level was stronger among overweight/obese children compared to normal weight children. Higher proportion of γ‐linolenic acid (β = 0.324, P = 0.017) and lower proportion of linoleic acid (β = −0.397, P = 0.005) in plasma CE were related to higher plasma irisin level among overweight/obese children, indicating the direct association of estimated D6D activity in plasma CE (β = 0.343, P = 0.011) with plasma irisin. Furthermore, higher proportion of oleic acid in plasma CE (β = 0.345, P = 0.012) and PL (β = 0.292, P = 0.033) and higher proportion of adrenic acid (β = 0.366, P = 0.008) and docosapentaenoic acid (β = 0.351, P = 0.010) in plasma PL were associated with higher plasma irisin level among overweight/obese children. Conclusion: Metabolically unfavourable plasma FA profile was associated with higher plasma irisin level especially in overweight/obese children, suggesting that excess body fat might modulate these relationships. [ABSTRACT FROM AUTHOR]

Objectives PNPLA3 I148M polymorphism (rs738409) has been strongly associated with liver fat content and plasma alanine aminotransferase ( ALT) levels in obese adults and children, but little is known about these relationships in normal weight individuals. We studied the associations and interactions of overweight and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up in children. Methods Subjects were a population sample of 481 Caucasian children aged 6-8 years examined at baseline and 419 children re-examined after 2-year follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419 children after 2-year follow-up were overweight. We assessed plasma ALT levels and other cardiometabolic risk factors and genotyped the PNPLA3 I148M polymorphism. Results Being overweight and carrying PNPLA3 148M allele were associated with increased ALT levels at baseline ( P = 0.002; P = 0.033) and after 2-year follow-up ( P < 0.001; P = 0.001). Being overweight ( P < 0.001) and carrying PNPLA3 148 M allele ( P = 0.001) were also associated with increase in ALT levels during 2-year follow-up. PNPLA3 148 M allele carriers had increased ALT levels at baseline ( P = 0.024 for interaction) and after 2-year follow-up ( P = 0.002 for interaction) as well as a larger increase in ALT levels during 2-year follow-up ( P = 0.002 for interaction) if they were overweight but not if they were normal weight. Further adjustment for clinical puberty, dietary factors, physical activity or sedentary behaviour had little or no effect on these associations. Conclusion PNPLA3 148 M allele carriers had higher plasma ALT levels and larger increase in ALT levels during follow-up than non-carriers only among overweight children. [ABSTRACT FROM AUTHOR]

In diabetes, defense systems against cellular stress are impaired. Heat shock proteins (HSPs) function primarily as molecular chaperones. Factors that raise tissue HSP levels may slow progression of diabetes and improve diabetic complications that also affect brain tissue. This study tested the effect of an 8-week exercise training on brain HSP response in rats with or without streptozotocin-induced diabetes (SID). In untrained animals, the HSP levels were not different between SID and non-diabetic groups. Endurance training, however, increased HSP72 and HSP90 protein in non-diabetic rats, whereas SID significantly decreased the effect of training on these HSPs. At the mRNA level, HSP60, HSP90 and GRP75 were increased due to training, whereas HSP72 mRNA was only increased in exercise-trained diabetic animals. Training or diabetes had no effect on protein carbonyl content, a marker of oxidative damage. Altogether, our findings suggest that endurance training increases HSP expression in the brain, and that experimental diabetes is associated with an incomplete HSP response at the protein level. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress., (Copyright © 2010 John Wiley & Sons, Ltd.)

Leptin regulates body weight, metabolism, and tissue adaptations to environmental stressors. We examined the association of single nucleotide polymorphism (SNP) of leptin promoter G-2548A (rs7799039) and leptin receptor Gln223Arg (rs1137101) with body composition, plasma leptin levels, and peak oxygen uptake (VO(2)peak) in response to 8 weeks of physical training in 48 male military conscripts. AA homozygotes of leptin promoter SNP-2548 showed higher body fat and BMI values than G allele carriers. Acute exercise decreased leptin levels in G allele carriers, but increased in AA homozygotes. Physical training significantly decreased BMI values and also a tendency for decreased plasma leptin levels was observed in all subjects. In G allele carriers, BMI loss was mainly due to decreased fat mass, whereas in AA homozygotes due to loss of fat-free mass. Training increased VO(2)peak in all subjects with most prominent effects in G allele carriers. Regarding leptin receptor SNP, there were no statistically significant differences in BMI values between the genotype groups at baseline or after physical training. Our results suggest that physical training-induced alterations in body composition and plasma leptin may be influenced by a genetic variation of leptin promoter but not of leptin receptor., (2010 John Wiley & Sons, Ltd.)

Background and Methods: Serum cholestanol and plant sterol ratios to cholesterol, surrogate markers of cholesterol absorption, are assumed to be high in type 1 diabetes (T1D), and the ratios of cholesterol precursor sterols (markers of synthesis) are assumed to be low reflecting downregulated cholesterol synthesis. To this end, we measured serum sterols with gas-liquid-chromatography in 56 men with T1D and in 18 controls to evaluate cholesterol metabolism. Subjects were categorised into tertiles by the cholestanol to cholesterol ratio of controls indicating low to high absorption of cholesterol., Results: The ratios of the synthesis markers were negatively related to the absorption markers in controls, but less consistently in T1D. The absorption markers were positively related to each other, but interrelation of the synthesis markers was less consistent in T1D. In the low absorbers the absorption markers were higher in T1D than in controls (e.g. sitosterol ratio 173 +/- 9 in T1D vs 135 +/- 11 10(2) x mmol/mol of cholesterol in controls, p < 0.05). In the high absorbers, the absorption markers were similar in T1D and controls, but the synthesis markers were higher in T1D than in controls (e.g. lathosterol ratio 154 +/- 10 in T1D vs 120 +/- 5 10(2) x mmol/mol of cholesterol in controls, p < 0.05)., Conclusions: Absorption and synthesis of cholesterol are less closely related to each other in T1D than in controls, but the markers of cholesterol absorption are interrelated also in T1D. Absorption of cholesterol is higher in T1D than in controls within the range of low absorption, but similar in those with relatively high cholesterol absorption.