The age differences and effect of mild cognitive impairment on perceptual-motor and executive functions.

It is unclear whether the decline in executive function (EF) and perceptual-motor function (PMF) found in older adults with mild cognitive impairment (MCI) is the result of a normal aging process or due to MCI. This study aimed to determine age-related and MCI-related cognitive impairments of the EF and PMF. The EF and PMF were investigated across four groups of 240 participants, 60 in each group, including early adult, middle adult, older adult, and older adult with probable MCI. The EF, working memory, inhibition, and cognitive flexibility were evaluated using digit span backward tasks, the Stroop color-word test, and the modified switching verbal fluency test, respectively. The PMF, visual perception, visuoconstructional reasoning, and perceptual-motor coordination were evaluated using the clock reading test, stick design test, and stick catching test, respectively. Group differences were found for all subdomains of EF and PMF (p < 0.05), except for perceptual-motor coordination, indicating that this subdomain could be maintained in older adults and was not affected by MCI. For the age difference, working memory, cognitive flexibility, visual perception, and visuoconstructional reasoning remained stable across middle adults and started to decline in older adults, while cognitive inhibition began to decrease in middle adults and it further declined in older adults. To control the confounding effect of education level, the results showed that only cognitive flexibility was further decreased in older adults with probable MCI compared to those without MCI (p < 0.05). In conclusion, cognitive inhibition decreased earlier in middle adults, whereas EF and PMF started to decline in older adults. Cognitive flexibility was the only MCI-sensitive cognitive function.

20-Hydroxyecdysone ameliorates metabolic and cardiovascular dysfunction in high-fat-high-fructose-fed ovariectomized rats.

BACKGROUND: Ecdysteroids are polyhydroxylated steroids present in invertebrates and plants. 20-Hydroxyecdysone (20E) is the most common and the main biologically active compound of ecdysteroids. Previous studies have demonstrated anabolic and metabolic effects of 20E in mammals. However, it is unknown whether 20E has a positive effect on all aspects of cardiometabolic syndrome. The aims of this study were to investigate the favorable effect and possible underlying mechanisms of 20E in a rat model of cardiometabolic syndrome (CMS) induced by a high-calorie diet combined with female sex hormone deprivation. METHODS: 20E (5 mg/kg, 10 mg/kg, or 20 mg/kg) or pioglitazone (PIO) (10 mg/kg) was intragastrically administered to sham-operated Sprague-Dawley female rats and ovariectomized rats fed a high-fat-high-fructose diet (OHFFD) for 8 weeks. The phenotypic characteristics of CMS, including central adiposity, blood pressure, serum lipid profile, glucose tolerance, insulin action on skeletal muscle glucose transport activity and hepatic protein expression, were determined. RESULTS: Some CMS characteristics were improved by 20E treatment. Rats treated with 20E had lower body weight, abdominal fat accumulation than rats treated with vehicle control without changes in total caloric intake and fat-free mass. OHFFD rats exhibited high blood pressure, but 20E-treated rats maintained normal blood pressure with a lower level of low-density lipoprotein (LDL)-cholesterol. Although 20E showed no positive effect on inducing insulin-mediated glucose transport in the skeletal muscle of OHFFD rats, 20E improved whole body glucose homeostasis. Analysis of protein expression in livers from 20E-treated rats revealed significantly increased expression of pAkt Ser473, pFOXO1 Ser256, pAMPKα Thr172, and FGF21. CONCLUSION: 20E treatment can alleviate cardiometabolic disorder caused by a high-fat-high-fructose diet and female sex hormone deprivation. In particular, 20E helps improve whole body insulin sensitivity in OHFFD rats, and the mechanisms that underlie this favorable effect are potentially mediated by the activation of AMPK and FGF21. The present study indicates that 20E could be an alternative therapeutic option for the prevention and alleviation of cardiometabolic syndrome.

Rosmarinic acid improves hypertension and skeletal muscle glucose transport in angiotensin II-treated rats.

BACKGROUND: Rosmarinic acid (RA) is a natural pure compound from herbs belonging to the Lamiaceae family, such as rosemary, sage, basil, and mint. The antioxidant, angiotensin-converting enzyme inhibitory, and vasodilatory effects of RA have been revealed. Angiotensin II (ANG II) is a potent agent that generates hypertension and oxidative stress. Hypertension and skeletal muscle insulin resistance are strongly related. The aim of this study was to evaluate the effects of acute and chronic RA treatment on blood pressure and skeletal muscle glucose transport in ANG II-induced hypertensive rats. METHODS: Eight-week-old male Sprague Dawley rats were separated into SHAM and ANG II-infused (250 ng/kg/min) groups. ANG II rats were treated with or without acute or chronic RA at 10, 20, or 40 mg/kg. At the end of the experiment, body weight, liver and heart weights, oral glucose tolerance, skeletal muscle glucose transport activity, and signaling proteins were evaluated. RESULTS: Both acute and chronic RA treatment decreased systolic, diastolic, and mean arterial blood pressure. Only acute RA at 40 mg/kg resulted in a reduction of fasting plasma glucose levels and an induction of skeletal muscle glucose transport activity. These effects might involve increased ERK activity in skeletal muscle. Meanwhile, chronic RA treatment with 10, 20, and 40 mg/kg prevented ANG II-induced hyperglycemia. CONCLUSIONS: Both acute and chronic RA treatment attenuated ANG II-induced cardiometabolic abnormalities in rats. Therefore, RA would be an alternative strategy for improving skeletal muscle glucose transport and protecting against ANG II-induced hypertension and hyperglycemia.

Voluntary exercise opposes insulin resistance of skeletal muscle glucose transport during liquid fructose ingestion in rats

We have recently reported that male rats given liquid fructose ingestion exhibit features of cardiometabolic abnormalities including non-obese insulin resistance with impaired insulin signaling transduction in skeletal muscle (Rattanavichit Y et al. Am J Physiol Regul Integr Comp Physiol 311: R1200-R1212, 2016). While exercise can attenuate obesity-related risks of cardiometabolic syndrome, the effectiveness and potential mechanism by which exercise modulates non-obese insulin resistance have not been fully studied. The present investigation evaluated whether regular exercise by voluntary wheel running (VWR) can reduce cardiometabolic risks induced by fructose ingestion. Moreover, the potential cellular adaptations following VWR on key signaling proteins known to influence insulin-induced glucose transport in skeletal muscle of fructose-ingested rats were investigated. Male Sprague-Dawley rats were given either water or liquid fructose (10% wt/vol) without or with access to running wheel for 6 weeks. We demonstrated that VWR restored insulin-stimulated glucose transport in the soleus muscle by improving the functionality of several signaling proteins, including insulin-stimulated IRBetaTyr1158/Tyr1162/Tyr1163 (82%), IRS-1 Tyr989 (112%), Akt Ser473 (56%), AS160 Thr642 (76%), and AS160 Ser588 (82%). These effects were accompanied by lower insulin-stimulated phosphorylation of IRS-1 Ser307 (37%) and JNK Thr183/Tyr185 (49%), without significant changes in expression of proteins in the renin-angiotensin system. Intriguingly, multiple cardiometabolic abnormalities were not observed in fructose-ingested rats with access to VWR. Collectively, this study demonstrates that the development of cardiometabolic abnormalities as well as insulin resistance of skeletal muscle and defective signaling molecules in rats induced by fructose ingestion could be opposed by VWR

Voluntary exercise opposes insulin resistance of skeletal muscle glucose transport during liquid fructose ingestion in rats.

We have recently reported that male rats given liquid fructose ingestion exhibit features of cardiometabolic abnormalities including non-obese insulin resistance with impaired insulin signaling transduction in skeletal muscle (Rattanavichit Y et al. Am J Physiol Regul Integr Comp Physiol 311: R1200-R1212, 2016). While exercise can attenuate obesity-related risks of cardiometabolic syndrome, the effectiveness and potential mechanism by which exercise modulates non-obese insulin resistance have not been fully studied. The present investigation evaluated whether regular exercise by voluntary wheel running (VWR) can reduce cardiometabolic risks induced by fructose ingestion. Moreover, the potential cellular adaptations following VWR on key signaling proteins known to influence insulin-induced glucose transport in skeletal muscle of fructose-ingested rats were investigated. Male Sprague-Dawley rats were given either water or liquid fructose (10% wt/vol) without or with access to running wheel for 6 weeks. We demonstrated that VWR restored insulin-stimulated glucose transport in the soleus muscle by improving the functionality of several signaling proteins, including insulin-stimulated IRß Tyr1158/Tyr1162/Tyr1163 (82%), IRS-1 Tyr989 (112%), Akt Ser473 (56%), AS160 Thr642 (76%), and AS160 Ser588 (82%). These effects were accompanied by lower insulin-stimulated phosphorylation of IRS-1 Ser307 (37%) and JNK Thr183/Tyr185 (49%), without significant changes in expression of proteins in the renin-angiotensin system. Intriguingly, multiple cardiometabolic abnormalities were not observed in fructose-ingested rats with access to VWR. Collectively, this study demonstrates that the development of cardiometabolic abnormalities as well as insulin resistance of skeletal muscle and defective signaling molecules in rats induced by fructose ingestion could be opposed by VWR.

Exercise Protects Against Defective Insulin Signaling and Insulin Resistance of Glucose Transport in Skeletal Muscle of Angiotensin II-Infused Rat.

Objectives: The present study investigated the impact of voluntary exercise on insulin-stimulated glucose transport and the protein expression and phosphorylation status of the signaling molecules known to be involved in the glucose transport process in the soleus muscle as well as other cardiometabolic risks in a rat model with insulin resistance syndrome induced by chronic angiotensin II (ANGII) infusion. Materials and Methods: Male Sprague-Dawley rats were assigned to sedentary or voluntary wheel running (VWR) groups. Following a 6-week period, rats in each group were subdivided and subcutaneously administered either normal saline or ANGII at 100 ng/kg/min for 14 days. Blood pressure, glucose tolerance, insulin-stimulated glucose transport and signaling proteins, including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), Akt, Akt substrate of 160 kDa (AS160), AMPKα, c-Jun NH2-terminal kinase (JNK), p38 MAPK, angiotensin converting enzyme (ACE), ANGII type 1 receptor (AT1R), ACE2, Mas receptor (MasR) and oxidative stress marker in the soleus muscle, were evaluated. Results: Exercise protected against the insulin resistance of glucose transport and defective insulin signaling molecules in the soleus muscle; this effect was associated with a significant increase in AMPK Thr172 (43%) and decreases in oxidative stress marker (31%) and insulin-induced p38 MAPK Thr180/Tyr182 (45%) and SAPK/JNK Thr183/Tyr185 (25%), without significant changes in expression of AT1R, AT2R, ACE, ACE2, and MasR when compared to the sedentary rats given ANGII infusion. At the systemic level, VWR significantly decreased body weight, fat weight, and systolic blood pressure as well as improved serum lipid profiles. Conclusion: Voluntary exercise can alleviate insulin resistance of glucose transport and impaired insulin signaling molecules in the soleus muscle and improve whole-body insulin sensitivity in rats chronically administered with ANGII.

Sex differences in the metabolic dysfunction and insulin resistance of skeletal muscle glucose transport following high fructose ingestion.

The role of high fructose ingestion (HFI) in the development of conditions mimicking human metabolic syndrome has mostly been demonstrated in male animals; however, the extent of HFI-induced metabolic alterations in females remains unclear. The present study investigated whether HFI-induced metabolic perturbations differ between sexes and whether HFI aggravates the metabolic disturbances under ovarian hormone deprivation. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were given either water or liquid fructose (10% wt/vol) for 6 wk. Blood pressure, glucose tolerance, insulin-stimulated glucose transport activity and signaling proteins, including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), Akt, Akt substrate of 160 kDa (AS160), AMPKα, JNK, p38 MAPK, angiotensin-converting enzyme (ACE), ANG II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) in skeletal muscle, were evaluated. We found that HFI led to glucose intolerance and hypertension in male and OVX rats but not in female rats with intact ovaries. Moreover, HFI did not induce insulin resistance in the skeletal muscle of female and OVX rats but impaired the insulin-stimulated glucose transport activity in the skeletal muscle of male rats, which was accompanied by lower insulin-stimulated IRS-1 Tyr989 (44%), Akt Ser473 (30%), and AS160 Ser588 (43%), and increases in insulin-stimulated IRS-1 Ser307 (78%), JNK Thr183/Tyr185 (69%), and p38 MAPK Thr180/Tyr182 (81%). The results from the present study show sex differences in the development of metabolic syndrome-like conditions and indicate the protective role of female sex hormones against HFI-induced cardiometabolic abnormalities.