Role of muscle IL-6 in gender-specific metabolism in mice

Molinero, Amalia; Fernandez-Perez, Antonio; Mogas, Aina; Giralt, Mercedes; Comes, Gemma; Fernández-Gayol, Olaya; Vallejo, Mario; Hidalgo, Juan

doi:10.1371/journal.pone.0173675

Cited by 31 publications

(22 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The antiandrogen Flutamide decreases the treadmill endurance of rats, but does not change O 2max and running economy 26 . Here, the exercise-induced submaximal O 2 and CO 2 up to O 2max were similar between sexes, as previously described 11 , 12 , 27 . Only one study demonstrated increased female submaximal O 2 during treadmill test, which further reinforces the hypothesis of females’ worst running economy 27 .…”

Section: Discussionsupporting

confidence: 82%

The exercise sex gap and the impact of the estrous cycle on exercise performance in mice

Aguiar

Speck

Amaral

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Exercise physiology is different in males and females. Females are poorly studied due to the complexity of the estrous cycle and this bias has created an exercise sex gap. Here, we evaluated the impact of sexual dimorphism and of the estrous cycle on muscle strength and running power of C57BL/6 mice. Like men, male mice were stronger and more powerful than females. Exercise-induced increase of O2 consumption (O2) and CO2 production (CO2) were equal between sexes, indicating that running economy was higher in males. Thermoregulation was also more efficient in males. In females, proestrus increased exercise O2 and CO2 at low running speeds (30–35% female O2max) and estrus worsened thermoregulation. These differences translated into different absolute and relative workloads on the treadmill, even at equal submaximal O2 and belt speeds. In summary, our results demonstrate the better muscle strength, running power and economy, and exercise-induced thermoregulation of males compared to females. Proestrus and estrus still undermined the running economy and exercise-induced thermoregulation of females, respectively. These results demonstrate an important exercise sex gap in mice.

show abstract

Section: Discussionsupporting

confidence: 82%

The exercise sex gap and the impact of the estrous cycle on exercise performance in mice

Aguiar

Speck

Amaral

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Most cytokines and chemokines involved with innate and stress-induced immunity are directly or indirectly inhibited by glucocorticoid receptor activation (27). IL-6 needs particular consideration because it has important metabolic effects that support lipolysis in adipose tissue and glucose homeostasis during exercise, some of these effects are general effects (21) and some sex specific (44). Exogenous IL-6 administration improves thermal tolerance and tissue protection from heat stroke (46).…”

Section: Andmentioning

confidence: 99%

Sex-dependent responses to exertional heat stroke in mice

Garcia

Mattingly

Robinson

et al. 2018

Journal of Applied Physiology

View full text Add to dashboard Cite

With increasing participation of females in endurance athletics and active military service, it is important to determine if there are inherent sex-dependent susceptibilities to exertional heat injury or heat stroke. In this study we compared responses of male and female adult mice to exertional heat stroke (EHS). All mice were instrumented for telemetry core temperature measurements and were exercise-trained for 3 wk before EHS. During EHS, environmental temperature was 37.5°C (35% RH) while the mice ran on a forced running wheel, using incremental increases in speed. The symptom-limited endpoint was loss of consciousness, occurring at ~42.2°C core temperature. Females ran greater distances (623 vs. 346 m, P < 0.0001), reached faster running speeds (7.2 vs. 5.1 m/min, P < 0.0001), exercised for longer times (177 vs. 124 min, P < 0.0001), and were exposed to greater internal heat loads (240 vs.160°C·min; P < 0.0001). Minimum Tc during hypothermic recovery was ~32.0°C in both sexes. Females lost 9.2% body weight vs. 7.5% in males ( P < 0.001). Females demonstrated higher circulating corticosterone (286 vs 183 ng/ml, P = 0.001, at 3 h), but most plasma cytokines were not different. A component of performance in females could be attributed to greater body surface area/mass and greater external power performance. However, there were significant and independent effects of sex alone and a crossed effect of "sex × power" on performance. These results demonstrate that female mice have greater resistance to EHS during exercise in hyperthermia and that these effects cannot be attributed solely to body size. NEW & NOTEWORTHY Female mice are surprisingly more resistant to exertional heat stroke than male mice. They run faster and longer and can withstand greater internal heat loads. These changes cannot be fully accounted for by increased body surface/mass ratio in females or on differences in aerobic performance. Although the stress-immune response in males and females was similar, females exhibited markedly higher plasma corticosteroid levels, which were sustained over 14 days of recovery.

show abstract

“…Indeed, tissue-specific knockout mice confirm that IL6 plays an important role in the obesity response (15)(16)(17)(18)(19)(20)(21)(22)(23).…”

mentioning

confidence: 97%

Regulation of adipose tissue inflammation by interleukin 6

Han

White

Perry

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

247

194

View full text Add to dashboard Cite

Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These opposite actions were associated with a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) with increased expression of the ADAM10/17 metalloprotease that promotes trans-signaling by the soluble IL6 receptor α. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.

show abstract

Role of muscle IL-6 in gender-specific metabolism in mice

Cited by 31 publications

References 51 publications

The exercise sex gap and the impact of the estrous cycle on exercise performance in mice

The exercise sex gap and the impact of the estrous cycle on exercise performance in mice

Sex-dependent responses to exertional heat stroke in mice

Regulation of adipose tissue inflammation by interleukin 6

Contact Info

Product

Resources

About