Even in the absence of weight gain, fructose rapidly causes liver damage that we suggest is secondary to endotoxemia and MT. HS relates to the duration of fructose consumption and total calories consumed. These data support fructose inducing both MT and ectopic fat deposition in primates.

Heat shock protein (HSP)70 decreases with age. Often aging is associated with coincident insulin resistance and higher blood glucose levels, which also associate with lower HSP70. We aimed to understand how these factors interrelate through a series of experiments using vervet monkeys (Chlorocebus aethiops sabaeous). Monkeys (n = 284, 4-25 years) fed low-fat diets showed no association of muscle HSP70 with age (r = .04, p = .53), but levels were highly heritable. Insulin resistance was induced in vervet monkeys with high-fat diets, and muscle biopsies were taken after 0.3 or 6 years. HSP70 levels were significantly greater after 0.3 years (+72%, p < .05) but were significantly lower following 6 years of high-fat diet (-77%, p < .05). Associations with glucose also switched from being positive (r = .44, p = .03) to strikingly negative (r = -.84, p < .001) with increasing insulin resistance. In conclusion, a low-fat diet may preserve tissue HSP70 and health with aging, whereas high-fat diets, insulin resistance, and genetic factors may be more important than age for determining HSP70 levels.

Heat shock proteins (HSPs) are molecular chaperones with roles in longevity and muscular preservation. We aimed to show elevating HSP70 improves indices of health span. Aged C57/BL6 mice acclimated to a western diet were randomized into: geranylgeranylacetone (GGA)-treated (100 mg/kg/d), biweekly heat therapy (HT), or control. The GGA and HT are well-known pharmacological and environmental inducers of HSP70, respectively. Assessments before and after 8 weeks of treatment included glycemic endpoints, body composition, and muscular endurance, power, and perfusion. An HT mice had more than threefold, and GGA mice had a twofold greater HSP70 compared with control. Despite comparable body compositions, both treatment groups had significantly better insulin sensitivity and insulin signaling capacity. Compared with baseline, HT mice ran 23% longer than at study start, which was significantly more than GGA or control. Hanging ability (muscular endurance) also tended to be best preserved in HT mice. Muscle power, contractile force, capillary perfusion, and innervation were not different. Heat treatment has a clear benefit on muscular endurance, whereas HT and GGA both improved insulin sensitivity. Different effects may relate to muscle HSP70 levels. An HSP induction could be a promising approach for improving health span in the aged mice.

Heat shock protein 70 (HSP70) protects cells from accumulating damaged proteins and age-related functional decline. We studied plasma and skeletal muscle (SkM) HSP70 levels in adult vervet monkeys (life span ≈ 25 years) at baseline and after 4 years (≈10 human years). Insulin, glucose, homeostasis model assessment scores, triglycerides, high-density lipoprotein and total plasma cholesterol, body weight, body mass index, and waist circumference were measured repeatedly, with change over time estimated by individual regression slopes. Low baseline SkM HSP70 was a proximal marker for developing insulin resistance and was seen in monkeys whose insulin and homeostasis model assessment increased more rapidly over time. Changes in SkM HSP70 inversely correlated with insulin and homeostasis model assessment trajectories such that a positive change in SkM level was beneficial. The strength of the relationship between changes in SkM HSP70 and insulin remained unchanged after adjustment for all covariates. Younger monkeys drove these relationships, with HSP70 alone being predictive of insulin changes with aging. Plasma and SkM HSP70 were unrelated and HSP70 release from peripheral blood mononuclear cells was positively associated with insulin concentrations in contrast to SkM. Results from aged humans confirmed this positive association of plasma HSP70 and insulin. In conclusion, higher levels of SkM HSP70 protect against insulin resistance development during healthy aging.

Blood viscosity (shear rates 100s -1 and 0.94s -1) and several of its major determinants (haematocrit, plasma fibrinogen and plasma viscosity) have been measured in 38 male insulin-treated diabetics, aged 18-50 years, and in 38 non-diabetic control subjects matched for age and smoking habit. Diabetics without fundoscopic retinopathy (n= 20) had higher mean blood viscosity than controls at the high shear rate (7.07 cP vs 6.75 cP, p < 0.05) and the low shear rate (21.2 cP vs 18.7 cP, p < 0.025). These differences persisted after correction of blood viscosity to a standard haematocrit, and were associated with increased plasma viscosity (1.41 cP vs 1.34 cP, p < 0.025) and plasma fibrinogen (2.9 g/L vs. 2.5 g/ L, p < 0.025). Diabetics with retinopathy (n = 18) had higher mean blood viscosity than diabetics without retinopathy at the high shear rate (7.53 cP vs 7.07 cP, p < 0.05) and the low shear rate (24.3 cP vs. 21.2cP, p < 0.05), associated with a higher haematocrit (p < 0.05).Blood viscosity and haematocrit correlated with the duration of diabetes (r > 0.32, p < 0.05).