Moderate aerobic training is safe and improves glucose intolerance induced by the association of high fat diet and air pollution.

Obesity and exposure to fine particulate matter (PM2.5) are risk factors for insulin resistance, to which physical exercise is the most powerful non-pharmacological strategy. However, public concern over whether exercise could be protective in a polluted environment exists. Therefore, evaluating the possible benefits of exercise in polluted conditions in different contexts (age, gender, and cardiometabolic health) is imperative. In this sense, muscle plays a major role in maintaining glucose homeostasis, and its oxidative status is closely affected during exercise. This study tested whether moderate aerobic training could alleviate the metabolic and oxidative impairment in the gastrocnemius induced by the combination of a high-fat diet (HFD) and PM2.5 exposure. Female mice (B6129SF2/J) received HFD (58.3% of fat) or standard diet, intranasal instillation of 20 µg residual oil fly ash (ROFA: inorganic portion of PM2.5), or saline seven times per week for 19 weeks. In the 13th week, animals were submitted to moderate training or remained sedentary. Trained animals followed a progressive protocol for 6 weeks, ending at swimming with 5% body weight of workload for 60 min, while sedentary animals remained in shallow water. Aerobic moderate training attenuated weight gain and glucose intolerance and prevented muscle and pancreatic mass loss induced by a HFD plus ROFA exposure. Interestingly, a HFD combined with ROFA enhanced the catalase antioxidant activity, regardless of physical exercise. Therefore, our study highlights that, even in polluted conditions, moderate training is the most powerful non-pharmacological treatment for obesity and insulin resistance.

Increased eHSP70-to-iHSP70 ratio in prediabetic and diabetic postmenopausal women: a biomarker of cardiometabolic risk.

Decreased estrogen levels in menopause are associated with anthropometric, metabolic, and inflammatory impairments, predisposing women to cardiometabolic risk factors such as diabetes. Menopause and type two diabetes (DM2) are marked by altered heat shock response (HSR), shown by decreased expression of the 70-kDa heat shock protein in the intracellular milieu (iHSP70). While iHSP70 plays an anti-inflammatory role, extracellular HSP70 (eHSP70) may mediate pro-inflammatory pathways and has been associated with insulin resistance in DM2. Considering the roles of these proteins according to localization, the eHSP70-to-iHSP70 ratio (H-index) has been proposed as a biomarker for HSR. We, therefore, evaluated whether this biomarker is associated with glycemic and inflammatory status in postmenopausal women. In this transversal study, 36 postmenopausal women were grouped according to fasting glycemia status as either the control group (normoglycemic, ≤ 99 mg/dL) or DM2 (prediabetic and diabetic, glycemia ≥ 100 mg/dL). DM2 group showed higher triglyceride/glucose (TyG) index and plasma atherogenic index (PAI), both of which are indicators of cardiometabolic risk. In addition, we found that the eHSP70-to-iHSP70 ratio (plasma/peripheral blood mononuclear cells-PBMC ratio) was higher in the DM2 group, compared with the control group. Furthermore, blood leukocyte and glycemia levels were positively correlated with the eHSP70-to-iHSP70 ratio in women that presented H-index values above 1.0 (a.u.). Taken together, our results highlight the eHSP70-to-iHSP70 ratio as a biomarker of altered HSR in DM2 postmenopausal women.

Adapted Murine Sepsis Score: Improving the Research in Experimental Sepsis Mouse Model.

The Murine Sepsis Score (MSS) is used to assess the severity of sepsis in rats and mice based on observational characteristics. The quantitative variables of glycemia, body weight, and temperature are predictors of severity in experimental models of sepsis. Therefore, our study sought to adapt the MSS with the same variables to indicate earlier the severity of the disease in murine models of the disease. Sepsis mice presented hypoglycemia, weight loss, and hypothermia. Therefore, these variables were included in the Adapted Murine Sepsis Score (A-MSS). The A-MASS presented 100% specificity and 87.5% sensibility been able to differentiate the early sepsis symptoms and its severity. The A-MSS allows an early and more complete diagnosis of sepsis in mice and might be considered as a procedure to improve the analysis of systemic sepsis dysfunction in murine experimental models.

Oxidative and Cellular Stress Markers in Postmenopause Women with Diabetes: The Impact of Years of Menopause.

Women live approximately one-third of their lives in postmenopause. Among postmenopausal women, type 2 diabetes mellitus (DM2) is one of the most prevalent chronic diseases. These conditions promote alterations in the oxidative, metabolic, and immune-inflammatory profiles marked by higher extracellular 72 kDa-heat shock protein (eHSP72). Here, we investigated whether the time of menopause is associated with oxidative cellular stress marker levels in postmenopausal women with DM2. Sixty-four women were recruited (56.7 ± 12.6 years old) in the pre- (n = 22) and postmenopause (n = 42) period, with (n = 19) or without DM2 (n = 45), and a fasting blood collection was made for the evaluation of metabolic, oxidative, and inflammatory markers. We found that menopause and DM2 influenced metabolic and oxidative parameters and presented synergistic effects on the plasma lipoperoxidation levels. Also, postmenopausal women had the highest eHSP72 concentration levels associated with the years in postmenopause. We conclude that the time of menopause impacts the markers of cellular stress and increases the risk of oxidative stress, mainly when it is associated with DM2.

Effects of aerobic and resistance exercise training associated with carnosine precursor supplementation on maximal strength and V̇O2max in rats with heart failure.

BACKGROUND: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was to test whether CET associated with supplementing carnosine precursors could present better responses in the functional capacity and biochemical variables of rats with HF. METHODS: Twenty-one male Wistar rats were subjected to myocardial infarction and allocated to three groups: sedentary (SED, n = 7), CET supplemented with placebo (CETP, n = 7), and CET with HF supplemented with ß-alanine and L-histidine (CETS, n = 7). The trained animals were submitted to a strength protocol three times per week. Aerobic training was conducted twice per week. The supplemented group received ß-alanine and L-histidine orally (250 mg/kg per day). RESULTS: Maximum oxygen uptake, running distance, time to exhaustion and maximum strength were higher in the CET-P group than that in the SED group and even higher in the CET-S group than that in the CET-P group (P < 0.01). CET-S showed lower oxidative stress and inflammation markers and higher heat shock protein 72 kDa content and mRNA expression for calcium transporters in the skeletal muscle compared to SED. CONCLUSION: CET together with ß-alanine and L-histidine supplementation in rats with HF can elicit adaptations in both maximum oxygen uptake, running distance, time to exhaustion, maximum strength, oxidative stress, inflammation and mRNA expression. Carnosine may influence beneficial adjustments in the cell stress response in the skeletal muscle and upregulate the mRNA expression of calcium transporters.

A single dose of eHSP72 attenuates sepsis severity in mice.

High levels of extracellular 72 kDa heat shock protein (eHSP72) can be detected in the serum of septic patients and are associated with increased oxidative profiles and elevated rates of mortality among these patients. However, a possible immunomodulatory role for this protein, resulting in tissue protection during sepsis, has never been assessed. In this study, we investigated whether eHSP72 administration could attenuate the severity of sepsis in a mouse peritonitis model. Animals (90-day-old male C57BL/6J mice) were divided into Sepsis (n = 8) and Sepsis + eHSP72 (n = 9) groups, which both received injections of 20% fecal solution [1 mg/g body weight (wt), intraperitoneal (i.p.)], to trigger peritonitis induced-sepsis, whereas a Control group (n = 7) received a saline injection. eHSP72 was administered (1.33 ng/g body wt) to the Sepsis+eHSP72 group, 12 h after sepsis induction. All animals were evaluated for murine sepsis score (MSS), hemogram, core temperature, and glycemia (before and 4, 12, and 24 h after sepsis induction). Treatment with eHSP72 promoted reduced sepsis severity 24 h after sepsis induction, based on MSS scores (Control = 1.14 ± 1.02; Sepsis = 11.07 ± 7.24, and Sepsis + eHSP72 = 5.62 ± 1.72, P < 0.001) and core temperatures (°C; Control = 37.48 ± 0.58; Sepsis = 35.17 ± 2.88, and Sepsis + eHSP72 = 36.94 ± 2.02; P = 0.006). eHSP72 treatment also limited the oxidative profile and respiratory dysfunction in mice with sepsis. Although sepsis modified glycemic levels and white and red blood cell counts, these variables were not influenced by eHSP72 treatment (P > 0.05). Finally, eHSP72 improved the survival rate after sepsis (P = 0.0371). Together, our results indicated that eHSP72 may ameliorate sepsis severity and possibly improve some sepsis indices in mice.

Ovariectomy predisposes female rats to fine particulate matter exposure's effects by altering metabolic, oxidative, pro-inflammatory, and heat-shock protein levels.

The reduction of estrogen levels, as a result of menopause, is associated with the development of metabolic diseases caused by alterations in oxidative stress (OS), inflammatory biomarkers, and 70-kDa heat-shock protein (HSP70) expression. Additionally, exposure to fine particulate matter air pollution modifies liver OS levels and predisposes organisms to metabolic diseases, such as type 2 diabetes (T2DM). We investigated whether ovariectomy affects hepatic tissue and alters glucose metabolism in female rats exposed to particulate air pollution. First, 24 female Wistar rats received an intranasal instillation of saline or particles suspended in saline 5 times per week for 12 weeks. The animals then received either bilateral ovariectomy (OVX) or false surgery (sham) and continued to receive saline or particles for 12 additional weeks, comprising four groups: CTRL, Polluted, OVX, and Polluted+OVX. Ovariectomy increased body weight and adiposity and promoted edema in hepatic tissue, hypercholesterolemia, glucose intolerance, and a pro-inflammatory profile (reduced IL-10 levels and increased IL-6/IL-10 ratio levels), independent of particle exposure. The Polluted+OVX group showed an increase in neutrophils and neutrophil/lymphocyte ratios, decreased antioxidant defense (SOD activity), and increased liver iHSP70 levels. In conclusion, alterations in the reproductive system predispose female organisms to particulate matter air pollution effects by affecting metabolic, oxidative, pro-inflammatory, and heat-shock protein expression.

Exercise Training under Exposure to Low Levels of Fine Particulate Matter: Effects on Heart Oxidative Stress and Extra-to-Intracellular HSP70 Ratio.

Fine particulate matter (PM2.5) promotes heart oxidative stress (OS) and evokes anti-inflammatory responses observed by increased intracellular 70 kDa heat shock proteins (iHSP70). Furthermore, PM2.5 increases the levels of these proteins in extracellular fluids (eHSP70), which have proinflammatory roles. We investigated whether moderate and high intensity training under exposure to low levels of PM2.5 modifies heart OS and the eHSP70 to iHSP70 ratio (H-index), a biomarker of inflammatory status. Male mice (n = 32), 30 days old, were divided into six groups for 12 weeks: control (CON), moderate (MIT) and high intensity training (HIT), exposure to 5 µg of PM2.5 daily (PM2.5), and moderate and high intensity training exposed to PM2.5 (MIT + PM2.5 and HIT + PM2.5 groups). The CON and PM2.5 groups remained sedentary. The MIT + PM2.5 group showed higher heart lipid peroxidation levels than the MIT and PM2.5 groups. HIT and HIT + PM2.5 showed higher heart lipid peroxidation levels and lower eHSP70 and H-index levels compared to sedentary animals. No alterations were found in heart antioxidant enzyme activity or iHSP70 levels. Moderate exercise training under exposure to low levels of PM2.5 induces heart OS but does not modify eHSP70 to iHSP70 ratio (H-index). High intensity exercise training promotes anti-inflammatory profile despite exposure to low levels of PM2.5.