Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue

Abstract

The aim of the present work was to study the consequences of chronic exercise training on factors involved in the regulation of mitochondrial remodeling and biogenesis, as well as the ability to produce energy and improve insulin sensitivity and glucose uptake in rat brown adipose tissue (BAT). Male Wistar rats were divided into two groups: (1) control group (C; n = 10) and (2) exercise-trained rats (ET; n = 10) for 8 weeks on a motor treadmill (five times per week for 50 min). Exercise training reduced body weight, plasma insulin, and oxidized LDL concentrations. Protein expression of ATP-independent metalloprotease (OMA1), short optic atrophy 1 (S-OPA1), and dynamin-related protein 1 (DRP1) in BAT increased in trained rats, and long optic atrophy 1 (L-OPA1) and mitofusin 1 (MFN1) expression decreased. BAT expression of nuclear respiratory factor type 1 (NRF1) and mitochondrial transcription factor A (TFAM), the main factors involved in mitochondrial biogenesis, was higher in trained rats compared to controls. Exercise training increased protein expression of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and AMP-activated protein kinase (pAMPK/AMPK ratio) in BAT. In addition, training increased carnitine palmitoyltransferase II (CPT II), mitochondrial F1 ATP synthase α-chain, mitochondrial malate dehydrogenase 2 (mMDH) and uncoupling protein (UCP) 1,2,3 expression in BAT. Moreover, exercise increased insulin receptor (IR) ratio (IRA/IRB ratio), IRA-insulin-like growth factor 1 receptor (IGF-1R) hybrids and p42/44 activation, and decreased IGF-1R expression and IR substrate 1 (p-IRS-1) (S307) indicating higher insulin sensitivity and favoring glucose uptake in BAT in response to chronic exercise training. In summary, the present study indicates that chronic exercise is able to improve the energetic profile of BAT in terms of increased mitochondrial function and insulin sensitivity.

Maternal exercise via exerkine apelin enhances brown adipogenesis and prevents metabolic dysfunction in offspring mice

“…Maternal adaptation to adverse environmental stimuli has been associated with various physiological changes in the offspring (11,23), establishing that maternal obesity is a major factor in the development of obesity and type 2 diabetes mellitus in offspring (23). Physical exercise is a prominent therapeutic tool to combat diet-induced obesity in adults (16,24), which can produce clinically important alterations in BAT morphology and mitochondrial activity (25). Despite these positive reports of exercise in enhancing UCP1 expression (26), PRDM16 expression (24), and mitochondrial biogenesis (25), there were also reports showing that exercise does not affect thermogenic and mitochondrial activity of BAT (27) or even down-regulated the BAT thermogenesis (28).…”

“…Physical exercise is a prominent therapeutic tool to combat diet-induced obesity in adults (16,24), which can produce clinically important alterations in BAT morphology and mitochondrial activity (25). Despite these positive reports of exercise in enhancing UCP1 expression (26), PRDM16 expression (24), and mitochondrial biogenesis (25), there were also reports showing that exercise does not affect thermogenic and mitochondrial activity of BAT (27) or even down-regulated the BAT thermogenesis (28). These inconsistent reports could be due to the difference in exercise types, intensity and duration, and animal physiological conditions (29), as well as the timing of sample collection following exercise (29).…”

Magnetic fields modulate metabolism and gut microbiome in correlation with Pgc‐1α expression: Follow‐up to an in vitro magnetic mitohormetic study

“…17,86,87 Adipose beiging is another accepted exercise adaptation that is likewise dependent on PGC-1α expression and associated changes in mitochondrial function and biogenesis. 88,89 In the short-term, the combination of PEMF treatment plus exercise (+E/+P) upregulated Pgc-1α and Ucp1 expression in WAT and BAT (Table 3) as well as produced alterations in gut microbiome composition indicative of reduced adiposity ( Figure 5). Obesity is associated with a high F/B ratio in mice 90 and humans.…”

Opposite Effects of Voluntary Physical Exercise on β3-Adrenergic Receptors in the White and Brown Adipose Tissue

“…The reduction of β3-adrenergic receptor mRNA concentrations in the brown adipose tissue of running rats was accompanied by an increase in UCP-1 expression. UCP-1 plays an important role in the metabolic adaptation of brown adipose tissue to exercise training and thermogenesis [40,41]. The signaling pathway of β3-adrenergic receptor stimulation in the brown adipose tissue is ultimately leading to the production of heat generated by uncoupling oxidative phosphorylation from ATP production via UCP-1 [42].…”

“…The signaling pathway of β3-adrenergic receptor stimulation in the brown adipose tissue is ultimately leading to the production of heat generated by uncoupling oxidative phosphorylation from ATP production via UCP-1 [42]. Nevertheless, next to findings of enhanced expression of UCP-1 following forced treadmill exercise [41,43], some authors failed to find any changes [44] or even a reduction of UCP-1 protein expression in the brown adipose tissue [45]. To our knowledge, there is no information on the changes in UCP-1 expression in response to voluntary exercise.…”