The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

Henstridge, Darren C.; Forbes, Josephine M.; Penfold, Sally A.; Formosa, Melissa F.; Dougherty, Sonia L; Gasser, Anna; Courten, Maximilian Pangratius J De; Cooper, Mark E.; Kingwell, Bronwyn A.

doi:10.1016/j.metabol.2010.01.027

Cited by 26 publications

(15 citation statements)

References 17 publications

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“…The mechanisms underlying the differential regulation of HSP-72 in diabetics and non-diabetic obese subjects are still unknown. In line with this, previous studies have report discrepancy in the expression levels of HSP-72 depending on the tissues [44,45]. …”

Section: Discussionsupporting

confidence: 67%

Immunohistochemical profiling of the heat shock response in obese non-diabetic subjects revealed impaired expression of heat shock proteins in the adipose tissue

et al. 2014

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BackgroundObesity is characterized by a chronic low-grade inflammation and altered stress responses in key metabolic tissues. Impairment of heat shock response (HSR) has been already linked to diabetes and insulin resistance as reflected by decrease in heat shock proteins (HSPs) expression. However, the status of HSR in non-diabetic human obese has not yet been elucidated. The aim of the current study was to investigate whether obesity triggers a change in the HSR pattern and the impact of physical exercise on this pattern at protein and mRNA levels.MethodsTwo groups of adult non-diabetic human subjects consisting of lean and obese (n = 47 for each group) were enrolled in this study. The expression pattern of HSP-27, DNAJB3/HSP-40, HSP-60, HSC-70, HSP72, HSP-90 and GRP-94 in the adipose tissue was primarily investigated by immunohistochemistry and then complemented by western blot and qRT-PCR in Peripheral blood mononuclear cells (PBMCs). HSPs expression levels were correlated with various physical, clinical and biochemical parameters. We have also explored the effect of a 3-month moderate physical exercise on the HSPs expression pattern in obese subjects.ResultsObese subjects displayed increased expression of HSP-60, HSC-70, HSP-72, HSP-90 and GRP-94 and lower expression of DNAJB3/HSP-40 (P < 0.05). No differential expression was observed for HSP-27 between the two groups. Higher levels of HSP-72 and GRP-94 proteins correlated positively with the indices of obesity (body mass index and percent body fat) and circulating levels of IFN-gamma-inducible protein 10 (IP-10) and RANTES chemokines. This expression pattern was concomitant with increased inflammatory response in the adipose tissue as monitored by increased levels of Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and RANTES (P < 0.05). Physical exercise reduced the expression of various HSPs in obese to normal levels observed in lean subjects with a parallel decrease in the endogenous levels of IL-6, TNF-α, and RANTES.ConclusionTaken together, these data indicate that obesity triggers differential regulation of various components of the HSR in non-diabetic subjects and a 3-month physical moderate exercise was sufficient to restore the normal expression of HSPs in the adipose tissue with concomitant attenuation in the inflammatory response.

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Section: Discussionsupporting

confidence: 67%

Immunohistochemical profiling of the heat shock response in obese non-diabetic subjects revealed impaired expression of heat shock proteins in the adipose tissue

et al. 2014

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“…In addition, we found that the degree of reduction of iHSP72 in the skeletal muscle was reduced in diabetic patients with lower adiposity. Henstridge et al (2010), by measuring the levels of HSP72 in young healthy human population free of hyperglycemia, demonstrated that iHSP72 protein expression in skeletal muscle is inversely correlated with percentage of body fat mass. These findings are consistent with rodent data suggesting that iHSP72 could be involved on the stimulation of fat oxidation (Gupte et al 2009b).…”

Section: Discussionmentioning

confidence: 99%

Divergence of intracellular and extracellular HSP72 in type 2 diabetes: does fat matter?

Rodrigues-Krause

Krause

O’Hagan

et al. 2012

Cell Stress and Chaperones

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“…In addition, oxygen uptake and fatty acid oxidation rates were lower, while fatty acid esterification rates higher in primary myocytes obtained from HSP72 −/− mice compared with WT [83] The hypothesis that Hsp72 stimulates fat oxidation with a consequent reduction in fat storage and adiposity gained further support in a clinical study, which observed lower expression of Hsp72 protein in human skeletal muscle associated with increased adiposity and decreased insulin sensitivity in healthy individuals [84]…”

Section: Hsp72 Mitochondria and Insulin Resistancementioning

confidence: 99%

Chaperoning to the metabolic party: The emerging therapeutic role of heat-shock proteins in obesity and type 2 diabetes

Henstridge

Whitham

Febbraio

2014

Molecular Metabolism

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BackgroundFrom their initial, accidental discovery 50 years ago, the highly conserved Heat Shock Proteins (HSPs) continue to exhibit fundamental roles in the protection of cell integrity. Meanwhile, in the midst of an obesity epidemic, research demonstrates a key involvement of low grade inflammation, and mitochondrial dysfunction amongst other mechanisms, in the pathology of insulin resistance and type 2 diabetes mellitus (T2DM). In particular, tumor necrosis factor alpha (TNFα), endoplasmic reticulum (ER) and oxidative stress all appear to be associated with obesity and stimulate inflammatory kinases such as c jun amino terminal kinase (JNK), inhibitor of NF-κβ kinase (IKK) and protein kinase C (PKC) which in turn, inhibit insulin signaling. Mitochondrial dysfunction in skeletal muscle has also been proposed to be prominent in the pathogenesis of T2DM either by reducing the ability to oxidize fatty acids, leading to the accumulation of deleterious lipid species in peripheral tissues such as skeletal muscle and liver, or by altering the cellular redox state. Since HSPs act as molecular chaperones and demonstrate crucial protective functions in stressed cells, we and others have postulated that the manipulation of HSP expression in metabolically relevant tissues represents a therapeutic avenue for obesity-induced insulin resistance.Scope of ReviewThis review summarizes the literature from both animal and human studies, that has examined how HSPs, particularly the inducible HSP, Heat Shock Protein 72 (Hsp72) alters glucose homeostasis and the possible approaches to modulating Hsp72 expression. A summation of the role of chemical chaperones in metabolic disorders is also included.Major ConclusionsTargeted manipulation of Hsp72 or use of chemical chaperiones may have clinical utility in treating metabolic disorders such as insulin resistance and T2DM.

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The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

Cited by 26 publications

References 17 publications

Immunohistochemical profiling of the heat shock response in obese non-diabetic subjects revealed impaired expression of heat shock proteins in the adipose tissue

Immunohistochemical profiling of the heat shock response in obese non-diabetic subjects revealed impaired expression of heat shock proteins in the adipose tissue

Divergence of intracellular and extracellular HSP72 in type 2 diabetes: does fat matter?

Chaperoning to the metabolic party: The emerging therapeutic role of heat-shock proteins in obesity and type 2 diabetes

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