Tissue-specific dysregulation of mitochondrial respiratory capacity and coupling control in colon-26 tumor-induced cachexia.

In addition to skeletal muscle dysfunction, cancer cachexia is a systemic disease involving remodeling of nonmuscle organs such as adipose and liver. Impairment of mitochondrial function is associated with multiple chronic diseases. The tissue-specific control of mitochondrial function in cancer cachexia is not well defined. This study determined mitochondrial respiratory capacity and coupling control of skeletal muscle, white adipose tissue (WAT), and liver in colon-26 (C26) tumor-induced cachexia. Tissues were collected from PBS-injected weight-stable mice, C26 weight-stable mice and C26 mice with moderate (10% weight loss) and severe cachexia (20% weight loss). The respiratory control ratio [(RCR) an index of oxidative phosphorylation (OXPHOS) coupling efficiency] was low in WAT during the induction of cachexia because of high nonphosphorylating LEAK respiration. Liver RCR was low in C26 weight-stable and moderately cachexic mice because of reduced OXPHOS. Liver RCR was further reduced with severe cachexia, where Ant2 but not Ucp2 expression was increased. Ant2 was inversely correlated with RCR in the liver (r = -0.547, P < 0.01). Liver cardiolipin increased in moderate and severe cachexia, suggesting this early event may also contribute to mitochondrial uncoupling. Impaired skeletal muscle mitochondrial respiration occurred predominantly in severe cachexia, at complex I. These findings suggest that mitochondrial function is subject to tissue-specific control during cancer cachexia, whereby remodeling in WAT and liver arise early and may contribute to altered energy balance, followed by impaired skeletal muscle respiration. We highlight an under-recognized role of liver and WAT mitochondrial function in cancer cachexia and suggest mitochondrial function of multiple tissues to be therapeutic targets.

Effect of Cadence on Time Trial Performance in Recreational Female Cyclists.

Graham, PL, Zoeller, RF, Jacobs, PL, and Whitehurst, MA. Effect of cadence on time trial performance in recreational female cyclists. J Strength Cond Res 32(6): 1739-1744, 2018-The impact of pedaling cadence on cycling performance remains unresolved especially in female cyclists. The purpose of this study was to determine the effect of cadence on time trial (TT) performance in recreational female cyclists. Ten recreational female cyclists volunteered to participate in this study. Subjects performed 3 exercise sessions: 1 to assess peak oxygen uptake (V[Combining Dot Above]O2peak) and 2 TTs. Cadence was randomly ordered and fixed for each TT (60 or 100 rpm), whereas power output (PO) was freely adjusted by the participant, as tolerated. Time trial time, heart rate (HR), blood lactate, PO, V[Combining Dot Above]O2, and ratings of perceived exertion were measured throughout the TTs. The major finding of this study was the significantly faster (p = 0.001) TT time during the 60-rpm condition (34:23 ± 4:21) vs. the 100-rpm condition (37:34 ± 5:53). Also the 60-rpm TT resulted in significant differences for HR (155.9 ± 3.97 vs. 161.2 ± 5.20 b·min, p = 0.04), gross efficiency, (21.1 ± 0.37 vs. 17.7 ± 0.85%, p < 0.001), and PO (147 ± 7.06 vs. 129 ± 10.62 W, p = 0.003). Thus, a slower cycling cadence was associated with greater mechanical efficiency and PO, resulting in significantly better performance in a TT. These results suggest that recreational female cyclists may benefit from adopting a low cadence during an 8-km TT.

Hippocampal Growth Factor and Myokine Cathepsin B Expression following Aerobic and Resistance Training in 3xTg-AD Mice.

Aerobic training (AT) can support brain health in Alzheimer's disease (AD); however, the role of resistance training (RT) in AD is not well established. Aside from direct effects on the brain, exercise may also regulate brain function through secretion of muscle-derived myokines. Aims. This study examined the effects of AT and RT on hippocampal BDNF and IGF-1 signaling, ß-amyloid expression, and myokine cathepsin B in the triple transgenic (3xTg-AD) model of AD. 3xTg-AD mice were assigned to one of the following groups: sedentary (Tg), aerobic trained (Tg+AT, 9 wks treadmill running), or resistance trained (Tg+RT, 9 wks weighted ladder climbing) (n = 10/group). Rotarod latency and strength were assessed pre- and posttraining. Hippocampus and skeletal muscle were collected after training and analyzed by high-resolution respirometry, ELISA, and immunoblotting. Tg+RT showed greater grip strength than Tg and Tg+AT at posttraining (p < 0.01). Only Tg+AT improved rotarod peak latency (p < 0.01). Hippocampal IGF-1 concentration was ~15% greater in Tg+AT and Tg+RT compared to Tg (p < 0.05); however, downstream signals of p-IGF-1R, p-Akt, p-MAPK, and p-GSK3ß were not altered. Cathepsin B, hippocampal p-CREB and BDNF, and hippocampal mitochondrial respiration were not affected by AT or RT. ß-Amyloid was ~30% lower in Tg+RT compared to Tg (p < 0.05). This data suggests that regular resistance training reduces ß-amyloid in the hippocampus concurrent with increased concentrations of IGF-1. Both types of training offered distinct benefits, either by improving physical function or by modifying signals in the hippocampus. Therefore, inclusion of both training modalities may address central defects, as well as peripheral comorbidities in AD.

Assessment of hip extensor and flexor strength two months after unilateral total hip arthroplasty.

This investigation assessed strength of the hip extensors and flexors when assistive devices and weight bearing are changing after total hip arthroplasty (THA). Eleven individuals (6 men, 5 women; mean age 74.45 +/- 4.88 years) with unilateral THA were evaluated isokinetically at 60 degrees x sec(-1) before surgery on the involved and uninvolved limbs. Each subject's involved limb was tested 60 days after surgery. Comparisons were made between involved and uninvolved limbs and between the involved limb before surgery and 60 days after surgery for both the hip extensors and flexors. Hip extensor and flexor strength before surgery on the involved side was 39% and 29% lower, respectively, compared with the uninvolved side. Sixty days after surgery, strength of the hip extensors and flexors improved 50% and 27%, respectively, compared with before surgery. Over the 60-day interval, the responsiveness of isokinetic testing was high for both muscle groups (range, 0.74-1.51). It would seem appropriate that intensive rehabilitation continue through at least the 60-day period and that isokinetic testing is an effective tool to monitor hip strength before and after surgery.

The benefits of a functional exercise circuit for older adults.

The physical benefits of a functional exercise circuit are not well known in an elderly population. The purpose of this study was to evaluate the effect of a functional exercise circuit on mobility and perceived health in the elderly. Subjects were 119 men and women (aged 74 [+/-4.2] years) who received pre- and posttests of mobility (e.g., sit to stand, get up and go, timed walk), flexibility (sit and reach), and balance (standing reach) and who completed the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A supervised functional exercise circuit that included 10 different upper- and lower-body exercises performed under time constraints was performed 3 times per week for 12 consecutive weeks. Paired t-tests showed significant differences at posttest for the get up and go (p < 0.001), standing reach (p < 0.001), sit and reach (p < 0.001), and selected items from the SF-36, including physical functioning (p < 0.001), pain (p = 0.001), vitality (p = 0.001), and number of doctor visits (p < 0.001). A functional exercise circuit such as the one employed in this study may offer promise as an effective means of promoting mobility and perceived health in older adults.