Exercise prevents HFD- and OVX-induced type 2 diabetes risk factors by decreasing fat storage and improving fuel utilization

Abstract

Previous studies suggest that the loss of estrogens increase one's risk for type 2 diabetes (T2D), and combining the loss of estrogens with a high‐fat diet (HFD) poses an even greater risk for T2D. The extent to which exercise can ameliorate the deleterious effects of estrogen loss combined with a HFD and the molecular mechanisms accounting for the whole body changes is currently unknown. Therefore, we fed female Wistar rats a standard diet or a HFD for 10 weeks. The rats fed the HFD were either ovariectomized (OVX) or their ovaries remained intact. A subset of the HFD/OVX rats also underwent exercise training on a motor‐driven treadmill. Exercise significantly reduced the total body weight gain, periuterine white adipose tissue (WAT) weight, hyperglycemia, and hyperinsulinemia. Additionally, the ability to store fat, as measured by lipoprotein lipase (LPL) in the WAT, was increased in the HFD/OVX group; however, exercise reduced the LPL levels. Furthermore, the combination of the HFD with OVX decreased the WAT citrate synthase protein level, which was increased with exercise. These data suggest that even during the combined HFD/OVX physiological state, exercise can decrease several risk factors associated with T2D, decrease fat storage, and increase fuel utilization.

Exercise improves high-fat diet- and ovariectomy-induced insulin resistance in rats with altered hepatic fat regulation

“…Furthermore, our study demonstrates that chronic exercise decreases the serum leptin levels, which is supported by other studies showing similar data ( Metz et al., 2016 ; Kohrt et al., 1996 ; Zoth et al., 2012 ). This decrease in serum leptin with chronic exercise is likely the result of the decreased adiposity in exercise-treated HFD/OVX rats, as previously published ( Gorres-Martens et al., 2018 ).…”

“…Adiponectin is thought to promote insulin sensitization and prevent insulin resistance ( Yamauchi et al., 2002 ). Thus, the increased adiponectin in the HFD/OVX group may provide protective effects against skeletal muscle and WAT insulin resistance despite consumption of a HFD, which has been shown previously ( Gorres-Martens et al., 2018 ). Alternatively, during obesity or high-fat feeding of male rodents, the adiponectin levels do not increase ( Arita et al., 1999 ; Metz et al., 2016 ), and skeletal muscle and WAT insulin resistance occur.…”

“…Since more than 70% of the blood glucose is disposed into the skeletal muscle ( Bjornholm and Zierath, 2005 ), numerous studies focus on metabolic alterations in the skeletal muscle, especially the insulin signaling pathway. While obesity and high-fat feeding in male rodents certainly lead to decreased activation of the skeletal muscle insulin signaling pathway and decreased glucose uptake ( Han et al., 1995 ; Zierath et al., 1997 ; Tremblay et al., 2001 ), we've recently shown that the insulin signaling pathway is not altered in the skeletal muscle or white adipose tissue (WAT) of female rodents fed a HFD, even when combined with OVX ( Gorres-Martens et al., 2018 ). However, high-fat feeding and/or OVX can certainly alter other physiological functions that lead to metabolic dysregulation.…”

“…We have previously shown that, unlike males fed a HFD, female rodents fed a HFD do not demonstrate decreased glucose uptake and altered insulin signaling in the skeletal muscle and WAT ( Gorres-Martens et al., 2018 ; Gorres et al., 1985 ). Thus, the present study focuses on the effects of a HFD in female rodents with and without endogenous estrogens on the liver, brain, and blood hormones.…”

Exercise-mediated angiogenesis

“…As standalone pathologies, both diabetes [30,35,48,69,70,77,78] and CHF [66][67][68][79][80][81] present with modest microvascular rarefaction, and those suffering with both are likely to have more pronounced rarefaction. To further complicate matters the metabolic response to these isolated pathologies is mixed, with evidence that diabetes may preserve [82] or increase oxidative demand of muscle, while CHF tends to present with a reduced oxidative capacity in locomotor muscles [83,84]. Diabetes [30,35,69,78,85,86] and CHF [81,84] induced rarefaction are both attenuated with increased activity, with concomitant increases in oxidative demand of skeletal muscles [86,87], although the functional benefits of these structural and enzymatic changes are still to be determined.…”