Insulin ameliorating endotoxaemia‐induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats

Duan, Kaipeng; Yu, Wenkui; Zhou, Lin; Tan, Shanjun; Bai, Xuekun; Gao, Tao; Xi, Fengchan; Li, Ning

doi:10.1111/cen.12610

Cited by 16 publications

(16 citation statements)

References 36 publications

(61 reference statements)

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“…Due to the close relationship between NF-κB pathway and inflammation18, inhibition of central NF-κB has an impact on the expression of hypothalamic proinflammatory cytokines and neuropeptides as shown in our results, which may further affect the muscle wasting. Although we can see some variation in food intake after NF-κB blockade, this was more likely due to neuropeptides alteration12, and should have little impact on peripheral muscle wasting as we have demonstrated in previous researches29.…”

Section: Discussionmentioning

confidence: 48%

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting

Duan

Chen

Zhao

et al. 2016

Sci Rep

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Growing evidence suggests acute skeletal muscle wasting is a key factor affecting nutritional support and prognosis in critical patients. Previously, plenty of studies of muscle wasting focused on the peripheral pathway, little was known about the central role. We tested the hypothesis whether central inflammatory pathway and neuropeptides were involved in the process. In lipopolysaccharide (LPS) treated rats, hypothalamic NF-κB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting. Central inhibition of nuclear factor kappa-B (NF-κB) pathway activation by infusion of an inhibitor (PS1145) can efficiently reduce muscle wasting as well as attenuate hypothalamic neuropeptides alteration. Furthermore, knockdown the expression of anorexigenic neuropeptide proopiomelanocortin (POMC) expression with a lentiviral vector containing shRNA can significantly alleviate LPS-induced muscle wasting, whereas hypothalamic inflammation or NF-κB pathway was barely affected. Taken together, these results suggest activation of hypothalamic POMC is pivotal for acute muscle wasting caused by endotoxemia. Neuropeptide POMC expression may have mediated the contribution of hypothalamic inflammation to peripheral muscle wasting. Pharmaceuticals with the ability of inhibiting hypothalamic NF-κB pathway or POMC activation may have a therapeutic potential for acute muscle wasting and nutritional therapy in septic patients.

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Section: Discussionmentioning

confidence: 48%

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting

Duan

Chen

Zhao

et al. 2016

Sci Rep

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“…LPS is most commonly injected intraperitoneally (i.p.) (Anderson et al, 2015; Arsenijevic and Montani, 2015; Arsenijevic D, 2000; Duan et al, 2014; Duan et al, 2015; Felies et al, 2004; Porter et al, 2000); however, Becskei et al found that i.p. but not subcutaneously (s.c.) injected LPS caused significant variation in hypothalamic cfos expression (Becskei et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, both TNFα and IFNγ were elevated 24 hours post-LPS injection (the time point used in the current study) whereas IL-1 and IL-6 were not (Arsenijevic D, 2000). AgRP expression is at its nadir and markers of muscle wasting are elevated at the 24 hour time point (Duan et al, 2014; Duan et al, 2015). ICV injection of IL-1β or TNFα induces anorexia and significantly decreases NPY mRNA expression suggesting that these cytokines may directly or indirectly target NPY/AgRP neurons (Arruda et al, 2010; Gayle et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…The endotoxin, lipopolysaccharide (LPS) induces illness anorexia and hypermetabolism leading to muscle wasting (Arsenijevic and Montani, 2015; Arsenijevic D, 2000; Becskei et al, 2008; Duan et al, 2014; Duan et al, 2015). Although chronic sepsis is most frequently associated with hyperglycemia, acute sepsis and LPS-induced endotoxemia can cause hypoglycemia in humans and animals (Feingold et al, 2012; Fischer et al, 1986; Krinsley, 2008; Malouf and Brust, 1985; McCallum et al, 1983; Wilmore, 1977).…”

Section: Introductionmentioning

confidence: 99%

“…interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), interferon gamma (INFγ)(Baile et al, 1981; Grossberg et al, 2010; Plata-Salaman et al, 1998; Plata-Salamán et al, 1988). TNFα, but not IL-1 or IL-6, is elevated 24 hours post-LPS injection when AgRP expression is at its nadir and markers of muscle wasting are elevated (Duan et al, 2014; Duan et al, 2015). Moreover, PEPCK expression was not decreased by LPS in TNFα receptor knockout mice suggesting a role for TNFα in LPS-induced hypoglycemia (Feingold et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose

et al. 2016

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A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24 hours and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24 hour time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus.

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Mild hypothermia ameliorates muscle wasting in septic rats associated with hypothalamic AMPK-induced autophagy and neuropeptides

Cao

Gao

et al. 2017

Biochemical and Biophysical Research Communications

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Insulin ameliorating endotoxaemia‐induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats

Abstract: Hypothalamic inflammation and neuropeptides are involved in the endotoxaemia-induced muscle wasting. Insulin treatment can reduce muscle wasting, which is associated with reduced hypothalamic inflammation and alteration of hypothalamic neuropeptides.

Cited by 16 publications

References 36 publications

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting

Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose

Mild hypothermia ameliorates muscle wasting in septic rats associated with hypothalamic AMPK-induced autophagy and neuropeptides

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