Table 2.

HSP70 and pathologic changes leading to cardiometabolic diseases.

Category	Finding	Reference
Protection of insulin resistance	Higher levels of skeletal muscle HSP70 protect against insulin resistance development during healthy aging.	[27]
	Heat treatment protects skeletal muscle from high-fat diet-induced insulin resistance. HSP induction in skeletal muscle could be a therapeutic approach to obesity-induced insulin resistance.	[28]
	Acute heat treatment can increase insulin-stimulated glucose uptake in aged skeletal muscle, with the underlying mechanism likely to be HSP72-mediated JNK inhibition.	[29]
	Intestinal secreted HSPs are one of the causes of insulin resistance when undergoing duodenal jejunal bypass.	[30]
Anti-inflammation	iHSP70 exerts potent anti-inflammatory effects and is associated with anti-insulin resistance in skeletal muscle. Increased eHSP70 is associated with inflammatory and oxidative stress conditions. An imbalance in the eHSP70/iHSP70 ratio is a contributing factor to the chronic inflammatory state that leads to the development of insulin resistance and type 2 diabetes.	[4]
Anti-apoptosis	iHSP70 inhibits apoptosis by inhibiting nuclear factor kappa B activation, nitric oxide production and superoxide dismutase activity. eHSP70 is released extracellularly under stress conditions and becomes an inflammatory mediator. Proposed eHSP70/iHSP70 as markers of inflammatory status.	[17]
	Inhibits stress-induced apoptotic signals.HSP70 synthesis act as an essential recovery mode for cellular survival and adaptation during lethal conditions.	[31]
	Sustained JNK activation promotes apoptosis.	[32]
	eHsp70 reduces apoptosis and necrosis of glial cells, but not neurons.eHsp70 reduces levels of the p53 protein apoptosis promoter (neuroprotective effect).	[33]
	Intranasal injection of recombinant Hsp70 reduced the level of apoptosis in the ischemic penumbra and stimulated axon formation.Exogenous Hsp70 significantly reduced light-induced apoptosis and necrosis of glial cells. Human recombinant Hsp70 may be translatable into clinical therapy.	[34]
Suppression of muscle atrophy	Exposure to heat stress increases HSP70 and suppresses muscle atrophy.	[35]
	Hyperthermia significantly decreases muscle atrophy markers (CD68, KLF, and MAFbx) and significantly increases muscle hypertrophy markers (AKT, mTOR, and HSP70).Hyperthermia is a viable treatment for reducing muscle wasting in diabetic patients.	[36]
Protein repair	Bathing in chloride hot springs enhances immunity such as NK cell activity, enhances protein repair function by HSP70, and has a psychological relaxing effect immediately after bathing.	[37]
	Serum-sensitive HSP70 is affected by exercise recovery, damaged tissue repair processes, and reduction of oxidative stress by inflammation. HSP70/90 expression is a potential biomarker for the preventive effects of exercise for the treatment of various diseases.	[38]