Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice

Wernstedt, Ingrid; Edgley, Amanda J.; Berndtsson, Anna; Faldt, Jenny; Bergström, Göran; Wallenius, Ville; Jansson, John‐Olov

doi:10.1152/ajpregu.00514.2005

Cited by 78 publications

(75 citation statements)

References 56 publications

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“…Furthermore, increases in UCP1 protein levels in WAT after exercise training or cold exposure are much less pronounced in IL‐6 knockout mice,63 while cold‐induced UCP1 levels in intrascapular BAT seem to be unaffected 64. In mice, cancer cachexia‐induced UCP1 expression in WAT is largely reduced in IL‐6‐receptor knockout mice 65.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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BackgroundIntramuscular fatty infiltration is generally associated with the accumulation of white adipocytes in skeletal muscle and unfavourable metabolic outcomes. It is, however, still unclear whether intramuscular adipocytes could also acquire a brown‐like phenotype. Here, we detected intramuscular expression of brown adipocyte markers during fatty infiltration in an obesity‐resistant mouse strain and extensively compared the potential of two different stem cell populations residing in skeletal muscle to differentiate into brown‐like adipocytes.MethodsFatty infiltration was induced using intramuscular glycerol or cardiotoxin injection in the tibialis anterior muscles of young or aged 129S6/SvEvTac (Sv/129) mice or interleukin‐6 (IL‐6) knockout mice, and the expression of general and brown adipocyte markers was assessed after 4 weeks. Fibro/adipogenic progenitors (FAPs) and myogenic progenitors were prospectively isolated using fluorescence‐activated cell sorting from skeletal muscle of male and female C57Bl6/6J and Sv/129 mice, and monoclonal and polyclonal cultures were treated with brown adipogenic medium. Additionally, FAPs were differentiated with medium supplemented or not with triiodothyronine.ResultsAlthough skeletal muscle expression of uncoupling protein 1 (Ucp1) was barely detectable in uninjected tibialis anterior muscle, it was drastically induced following intramuscular adipogenesis in Sv/129 mice and further increased in response to beta 3‐adrenergic stimulation. Intramuscular Ucp1 expression did not depend on IL‐6 and was preserved in aged skeletal muscle. Myogenic progenitors did not form adipocytes neither in polyclonal nor monoclonal cultures. Fibro/adipogenic progenitors, on the other hand, readily differentiated into brown‐like, UCP1+ adipocytes. Uncoupling protein 1 expression in differentiated FAPs was regulated by genetic background, sex, and triiodothyronine treatment independently of adipogenic differentiation levels.ConclusionsIntramuscular adipogenesis is associated with increased Ucp1 expression in skeletal muscle from obesity‐resistant mice. Fibro/adipogenic progenitors provide a likely source for intramuscular adipocytes expressing UCP1 under control of both genetic and hormonal factors. Therefore, FAPs constitute a possible target for therapies aiming at the browning of intramuscular adipose tissue and the metabolic improvement of skeletal muscle affected by fatty infiltration.

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Section: Discussionmentioning

confidence: 99%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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“…Another potential mechanism through which IL-6 could promote increased insulin sensitivity and glucose metabolism is an increase in GLUT1 expression, which is observed in the WAT and hearts of mice receiving BAT. The increase in GLUT1 could be stimulated by the increase in IL-6 and/or FGF21, as IL-6 (24,33,(36)(37)(38) and FGF21 (21,22,39) have been shown to increase GLUT1 expression in cultured brown adipocytes and 3T3-L1 cells, respectively.…”

Section: Discussionmentioning

confidence: 99%

Brown adipose tissue regulates glucose homeostasis and insulin sensitivity

Stanford

Middelbeek²,

Townsend³

et al. 2012

J. Clin. Invest.

998

871

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Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age-and sex-matched recipient mice. By 8-12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, and a complete reversal of high-fat diet-induced insulin resistance. Increasing the quantity of BAT transplanted into recipient mice further improved the metabolic effects of transplantation. BAT transplantation increased insulin-stimulated glucose uptake in vivo into endogenous BAT, white adipose tissue (WAT), and heart muscle but, surprisingly, not skeletal muscle. The improved metabolic profile was lost when the BAT used for transplantation was obtained from Il6-knockout mice, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity. These findings reveal a previously under-appreciated role for BAT in glucose metabolism.

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“…26 Mice do not increase their oxygen consumption by more than 2-fold, even at peak exercise 27 or after cage-switch stress. 28 Murine heart rate is predominantly under sympathetic control 29 and does not increase by more than 50% at maximal exercise. 30 Mice, therefore, may need less coronary reserve than humans to respond to increased myocardial oxygen requirements.…”

Section: Raher Et Al Murine Contrast Echocardiographymentioning

confidence: 99%

In Vivo Characterization of Murine Myocardial Perfusion With Myocardial Contrast Echocardiography

et al. 2007

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Background-The ability to noninvasively evaluate murine myocardial blood flow (MBF) in vivo would provide an important tool for cardiovascular research. Myocardial contrast echocardiography (MCE) has been used to measure MBF; however, it has not been validated in mice. This study assesses whether MCE can evaluate MBF at rest and after vasodilation and measure the maximal augmentation (coronary reserve) of MBF in mice. Wild-type (WT) and nitric oxide synthase 3 (NOS3)-deficient (NOS3 Ϫ/Ϫ ) mice were studied. Methods and Results-MCE was performed at baseline and after intravenous infusion of acetylcholine or adenosine.Definity contrast agent was infused, and parasternal views were acquired in real-time mode. Replenishment curves of myocardial contrast were obtained, and rates of signal rise (␤) and plateau intensity (A) were calculated. MBF estimated by the product of A and ␤ (A␤) was compared with that measured with fluorescent microspheres. MCE analysis was feasible in 98% (52/53) of mice. MBF measured by microspheres increased with adenosine and correlated closely with A␤. There was no difference in MCE-derived MBF between WT and NOS3 Ϫ/Ϫ mice at rest. Adenosine infusion increased MBF by 3.0Ϯ0.6-fold in NOS3 Ϫ/Ϫ mice and 2.5Ϯ0.3-fold in WT (Pϭ0.58 between genotypes). Acetylcholine induced an increase of 2.4Ϯ0.2-fold in MBF in WT mice but did not increase MBF in NOS3 Ϫ/Ϫ mice (PϽ0.0005 versus WT). Conclusions-MBF, coronary reserve, and vasodilator responses can be evaluated accurately in the intact mouse by MCE.This method demonstrated a preserved coronary response to adenosine but an impaired acetylcholine-induced vasodilation in NOS3 Ϫ/Ϫ mice compared with WT mice.

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Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice

Cited by 78 publications

References 56 publications

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Brown adipose tissue regulates glucose homeostasis and insulin sensitivity

In Vivo Characterization of Murine Myocardial Perfusion With Myocardial Contrast Echocardiography

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