The dance of proteostasis and metabolism: Unveiling the caloristatic controlling switch.

The heat shock response (HSR) is an ancient and evolutionarily conserved mechanism designed to restore cellular homeostasis following proteotoxic challenges. However, it has become increasingly evident that disruptions in energy metabolism also trigger the HSR. This interplay between proteostasis and energy regulation is rooted in the fundamental need for ATP to fuel protein synthesis and repair, making the HSR an essential component of cellular energy management.

Resolution of inflammation in chronic disease via restoration of the heat shock response (HSR).

Effective resolution of inflammation via the heat shock response (HSR) is pivotal in averting the transition to chronic inflammatory states. This transition characterizes a spectrum of debilitating conditions, including insulin resistance, obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular ailments. This manuscript explores a range of physiological, pharmacological, and nutraceutical interventions aimed at reinstating the HSR in the context of chronic low-grade inflammation, as well as protocols to assess the HSR.

Heat shock response during the resolution of inflammation and its progressive suppression in chronic-degenerative inflammatory diseases.

The heat shock response (HSR) is a crucial biochemical pathway that orchestrates the resolution of inflammation, primarily under proteotoxic stress conditions. This process hinges on the upregulation of heat shock proteins (HSPs) and other chaperones, notably the 70 kDa family of heat shock proteins, under the command of the heat shock transcription factor-1. However, in the context of chronic degenerative disorders characterized by persistent low-grade inflammation (such as insulin resistance, obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases) a gradual suppression of the HSR does occur.

Air pollution combined with high-fat feeding aggravates metabolic and cardiovascular diseases: A dangerous, oxidative, and immune-inflammatory association.

Unlabelled: Obesity and particulate air pollutant (PM) are important risk factors for cardiometabolic diseases. PM exacerbates insulin resistance and lipid ectopic deposition in obese animals. The inorganic fraction of PM the Residual Oil Fly Ash (ROFA), is related to cardiovascular events, by enhancing the generation of reactive species, inflammatory cytokines, and leukocyte activation.

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.

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.

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).

Ovariectomy reduces the cardiac cytoprotection in rats exposed to particulate air pollutant.

Fine particulate matter (PM) has been considered a risk factor for cardiovascular diseases by inducing an oxidative and inflammatory phenotype. Besides, the reduction of 17β-estradiol (E2) levels during menopause is a natural risk for cardiovascular outcomes. During the E2 downfall, there is a high requirement of the 70-kDa heat shock proteins (HSP70), which present essential antioxidant, anti-inflammatory, and anti-senescence roles.

Ovariectomy enhances female rats' susceptibility to metabolic, oxidative, and heat shock response effects induced by a high-fat diet and fine particulate matter.

Obesity and exposure to fine particulate matter (air pollutant PM) are important risk factors for metabolic and cardiovascular diseases. They are also related to early menopause. The reduction of 17β-estradiol (E2) levels during female climacteric, marked by menopause, is of significant concern because of its imminent influence on metabolism, redox and inflammatory status.

Are Heat Shock Proteins an Important Link between Type 2 Diabetes and Alzheimer Disease?

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.

Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: lessons from basic research (inclusive bats), light on conceivable therapies.

The major risk factors to fatal outcome in COVID-19 patients, i.e., elderliness and pre-existing metabolic and cardiovascular diseases (CVD), share in common the characteristic of being chronic degenerative diseases of inflammatory nature associated with defective heat shock response (HSR).

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.

The association of subchronic exposure to low concentration of PM and high-fat diet potentiates glucose intolerance development, by impairing adipose tissue antioxidant defense and eHSP72 levels.

The subchronic exposure to fine particulate matter (PM) and high-fat diet (HFD) consumption lead to glucose intolerance by different mechanisms involving oxidative stress and inflammation. Under stressful conditions, the cells exert a heat shock response (HSR), by releasing the 72-kDa heat shock proteins (eHSP72), fundamental chaperones. The depletion of the HSR can exacerbate the chronic inflammation.

Chaperone duality: the role of extracellular and intracellular HSP70 as a biomarker of endothelial dysfunction in the development of atherosclerosis.

The 70-kDa heat shock proteins (HSP70) may provide relevant information about the endothelial dysfunction in cardiovascular diseases. Located in the intracellular milieu (iHSP70), they are essential chaperones that inhibit nuclear factor kappa B activation, stimulate nitric oxide production and superoxide dismutase activity, and inhibit apoptosis. However, under stressful conditions, HSP70 can be released into the extracellular medium (eHSP70) and act as an inflammatory mediator.

Chronic heat treatment positively impacts metabolic profile of ovariectomized rats: association with heat shock response pathways.

Low estrogen levels may predispose women to increased bodyweight and dyslipidemia. Previous studies from our laboratory suggest an involvement of depressed heat shock response (HSR) in this scenario because estrogen potently stimulates HSR. As heat treatment induces the expression of the anti-inflammatory heat shock proteins of the 70-kDa family (HSP70) and its accompanying HSR, we aimed to investigate whether chronic heat treatment promotes beneficial effects on biometric, lipid profile, oxidative stress, and HSR in ovariectomized rats.

Inflammation, oxidative stress and altered heat shock response in type 2 diabetes: the basis for new pharmacological and non-pharmacological interventions.

Type 2 diabetes mellitus (DM2) is a chronic disease characterised by variable degrees of insulin resistance and impaired insulin secretion. Besides, several pieces of evidence have shown that chronic inflammation, oxidative stress, and 70 kDa heat shock proteins (HSP70) are strongly involved in DM2 and its complications, and various pharmacological and non-pharmacological treatment alternatives act in these processes/molecules to modulate them and ameliorate the disease. Besides, uncontrolled hyperglycaemia is related to several complications as diabetic retinopathy, neuropathy and hepatic, renal and cardiac complications.

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.

Effects of High-Fat Diet on eHSP72 and Extra-to-Intracellular HSP70 Levels in Mice Submitted to Exercise under Exposure to Fine Particulate Matter.

Obesity, air pollution, and exercise induce alterations in the heat shock response (HSR), in both intracellular 70 kDa heat shock proteins (iHSP70) and the plasmatic extracellular form (eHSP72). Extra-to-intracellular HSP70 ratio (H-index = eHSP70/iHSP70 ratio) represents a candidate biomarker of subclinical health status. This study investigated the effects of moderate- and high-intensity exercise in the HSR and oxidative stress parameters, in obese mice exposed to fine particulate matter (PM).

Detectable levels of eHSP72 in plasma are associated with physical activity and antioxidant enzyme activity levels in hypertensive subjects.

Previous studies reported that extracellular HSP72 (eHSP72) correlates with poor prognosis, markers of vascular dysfunction, and the severity of cardiovascular diseases, associated with a systemic oxidative and inflammatory profile. On the other hand, eHSP72 may represent immune-regulatory signaling that is related to exercise benefits, but the association between physical activity levels and eHSP72 levels is not established. Thus, since regular physical activity may avoid oxidative stress and inflammation, we investigate whether detectable levels of eHSP72 in plasma are associated with physical activity and antioxidant enzyme activity levels in hypertensive subjects.

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 (PM) promotes heart oxidative stress (OS) and evokes anti-inflammatory responses observed by increased intracellular 70 kDa heat shock proteins (iHSP70). Furthermore, PM 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 PM modifies heart OS and the eHSP70 to iHSP70 ratio (H-index), a biomarker of inflammatory status.

Fine particulate matter potentiates type 2 diabetes development in high-fat diet-treated mice: stress response and extracellular to intracellular HSP70 ratio analysis.

Exposure to fine particulate matter (PM) air pollution is a risk factor for type 2 diabetes (T2DM). We argue whether the potentiating effect of PM over the development of T2DM in high-fat diet (HFD)-fed mice would be related to modification in cell stress response, particularly in antioxidant defenses and 70-kDa heat shock proteins (HSP70) status. Male mice were fed standard chow or HFD for 12 weeks and then randomly exposed to daily nasotropic instillation of PM for additional 12 weeks under the same diet schedule, divided into four groups (n = 14-15 each): Control, PM, HFD, and HFD + PM were evaluated biometric and metabolic profiles of mice, and cellular stress response (antioxidant defense and HSP70 status) of metabolic tissues.

The chaperone balance hypothesis: the importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management.

Recent evidence shows divergence between the concentrations of extracellular 70 kDa heat shock protein [eHSP70] and its intracellular concentrations [iHSP70] in people with type 2 diabetes (T2DM). A vital aspect regarding HSP70 physiology is its versatility to induce antagonistic actions, depending on the location of the protein. For example, iHSP70 exerts a powerful anti-inflammatory effect, while eHSP70 activates proinflammatory pathways.