Hsp70 plays an important role in high-fat diet induced gestational hyperglycemia in mice

Abstract

Gestational diabetes mellitus (GDM) has emerged as an epidemic disease during the last decade, affecting about 2 to 5% pregnant women. Even among women who have gestational hyperglycemia may also be positively related to adverse outcomes as GDM. Since heat shock protein (Hsp) 70 has been reported to be associated with diabetes and insulin resistance and its expression was reported to be negatively regulated by the membrane-permeable Hsp70 inhibitor MAL3-101 while positively regulated by the Hsp70 activator BGP-15, we investigated whether Hsp70 played a role in a gestational hyperglycemia mouse model. Mice were divided into non-pregnant and pregnant groups, and each comprised three subgroups: control, high-fat diet (HFD) + MAL3-101, and HFD + BGP-15. We examined the serum levels of triglycerides, total cholesterol, glucose, and insulin, as well as conducted thermal detection of brown adipose tissue (BAT). The role of Hsp70 in BAT apoptosis was also investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspase-3 staining. Higher serum level of Hsp70 was associated with increased bodyweight gain after pregnancy in mice fed HFD. Circulating Hsp70 was elevated in control pregnant mice compared to control non-pregnant mice. BGP-induced serum Hsp70 expression reduced triglycerides, total cholesterol, glucose, and insulin levels in the serum. Additionally, thermal detection of BAT, TUNEL, and caspase-3 staining revealed relationship correlation between Hsp70 and BAT functions. Hsp70 level is associated with hyperglycemia during pregnancy. Our results support the role of Hsp70 in facilitating BAT activities and protecting BAT cells from apoptosis via caspase-3 pathway.

Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome

“…To study the effect of BGP-15 in gestational diabetes, mellitus female C57BL/6 mice were involved in the study and mated with non-diabetic male mice to cause pregnancy. Brown adipose tissue was removed at the end of the 15th week [56].…”

Factors that Affect Pancreatic Islet Cell Autophagy in Adult Rats: Evaluation of a Calorie-Restricted Diet and a High-Fat Diet

“…Dietary intervention can affect glucose tolerance via autophagy[ 8 ]. For example, a high-fat diet has been proven to increase insulin resistance and thereby promote the prevalence of T2DM[ 9 , 10 ], and HFD intervention in young mice (8 weeks old) was shown to increase autophagic flux in pancreatic β cells both in and ex vivo[ 11 ]. A calorie-restricted diet (CRD) is considered the most robust non-genetic autophagic promoter and lifespan-extending method in many species[ 12 ].…”

Preventive and promotive effects of habitual hot spa-bathing on the elderly in Japan

“…Body-warming by spa-bathing may lead to the increased circulation of heat shock proteins. The serum level of Hsp-70 only increases among women with diabetes mellitus 12 , and plays a causative role in gestational hyperglycemia 13 , 14 . Therefore, body-warming can cause specific responses involving heat shock proteins in women.…”