Reduced vagal control of the heart in high-fat diet mice: a potential role of increased butyrylcholinesterase

Hartnett, Sigurd; Gao, Hongbo; Schnack, Sabrina; Li, Yifan

doi:10.14814/phy2.12609

Cited by 4 publications

(5 citation statements)

References 47 publications

(78 reference statements)

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“…Following centrifugation at 10,000 xg for 10 minutes, protein concentration in the supernatant of homogenates was determined and normalized. IL-6 protein and other protein of interest in the muscle samples were determined using standard Western blot as described previously[10, 11] with appropriate antibodies.…”

Section: Methodsmentioning

confidence: 99%

Skeletal muscle secretion of IL-6 is muscle type specific: Ex vivo evidence

Liang¹,

Drazick²,

Gao³

et al. 2018

Biochemical and Biophysical Research Communications

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Emerging evidence indicates that skeletal muscle possesses endocrine function to secret myokines. Interleukin 6 (IL-6) is a well-characterized myokine that is involved in regulation of metabolism and muscle function. Metabolism type and contractile dynamics vary in different muscle types. It is not clear, however, if IL-6 secretion differs in different muscle types. In this study, we first established an ex vivo approach to test the inducible muscle secretion. Freshly isolated muscles were incubated in Krebs solution at 37 °C with oxygen supply. Secreted IL-6 in the incubation media was measure using Western blot and ELISA assay. We first confirmed that the IL-6 release was inducible by treating the incubated muscle with a cytokine stimulant. We demonstrated that physiological temperature (37 °C) and O supply were essential for the induction of IL-6 release from the incubated muscle, suggesting it is a controlled secretion rather than a spontaneous leak. Using this approach, we found that IL-6 release was only inducible from soleus muscle but not EDL muscle. We further showed that IL-6 protein level was higher in slow oxidative muscle fibers. Moreover, we showed that EDL, although lacks of IL-6 release, surely has inducible secretory function that had different secretory pattern from soleus.

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Section: Methodsmentioning

confidence: 99%

Skeletal muscle secretion of IL-6 is muscle type specific: Ex vivo evidence

Liang¹,

Drazick²,

Gao³

et al. 2018

Biochemical and Biophysical Research Communications

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“…Reductions in parasympathetic tone occurred early and often preceded increased sympathetic activity in both animal models of and patients with heart failure ( Ishise et al, 1998 ; Motte et al, 2005 ). Therefore, these types of investigations into the early influence of diets may help elucidate the neuromechanism(s) through which high fat diet contributes to the pathogenesis of cardiovascular disease ( Fleming, 2002 ; Hartnett et al, 2015 ).…”

Section: The Influence Of Metabolic Disruptions On Parasympathetic Fumentioning

confidence: 99%

Interplay Between Systemic Metabolic Cues and Autonomic Output: Connecting Cardiometabolic Function and Parasympathetic Circuits

2021

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There is consensus that the heart is innervated by both the parasympathetic and sympathetic nervous system. However, the role of the parasympathetic nervous system in controlling cardiac function has received significantly less attention than the sympathetic nervous system. New neuromodulatory strategies have renewed interest in the potential of parasympathetic (or vagal) motor output to treat cardiovascular disease and poor cardiac function. This renewed interest emphasizes a critical need to better understand how vagal motor output is generated and regulated. With clear clinical links between cardiovascular and metabolic diseases, addressing this gap in knowledge is undeniably critical to our understanding of the interaction between metabolic cues and vagal motor output, notwithstanding the classical role of the parasympathetic nervous system in regulating gastrointestinal function and energy homeostasis. For this reason, this review focuses on the central, vagal circuits involved in sensing metabolic state(s) and enacting vagal motor output to influence cardiac function. It will review our current understanding of brainstem vagal circuits and their unique position to integrate metabolic signaling into cardiac activity. This will include an overview of not only how metabolic cues alter vagal brainstem circuits, but also how vagal motor output might influence overall systemic concentrations of metabolic cues known to act on the cardiac tissue. Overall, this review proposes that the vagal brainstem circuits provide an integrative network capable of regulating and responding to metabolic cues to control cardiac function.

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“…Muscle tissues were homogenized in RIPA buffer containing a protease inhibitor cocktail (Santa Cruz, Dallas, TX) and phosphatase inhibitor (Research Product International, Mount Prospect, IL). Protein concentration of samples were determined by a standard BCA assay and the samples were subjected to standard western blot protocol, as described previously (Hartnett et al 2015). Proteins that were transferred onto the membranes were immunoblotted using the following primary antibodies: AKT, phosphorylated AKT (Ser473), FoxO3, phosphorylated FoxO3 (Ser253), LC3, IRS1, AMPKa and phosphorylated AMPKa (Thr172) (Cell Signaling Technologies, Danvers, MA); GAPDH, Ubiquitin, pERK and ERK (Santa Cruz Inc., Santa Cruz, CA); MurF1 and Atrogin1 (GeneTex, Irvine, CA); and PGC1a (Millipore-Sigma, St. Louis, MO).…”

Section: Western Blotmentioning

confidence: 99%

Distinct signal transductions in fast- and slow- twitch muscles upon denervation

Gao

2018

Physiol Rep

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Denervation induces skeletal muscle atrophy, which primarily impairs oxidative slow twitch fibers. The underlying mechanism of this phenomenon, however, remains to be addressed. We hypothesize that denervation‐induced fiber‐specific atrophy may result from the distinct activities of different signaling pathways that are involved in protein synthesis and degradation in fast‐ and slow‐twitch fibers. In this study, 1‐month‐old male mice were subjected to unilateral sciatic denervation for 4 days. Fast‐twitch muscle extensor digitorum longus (EDL) and slow‐twitch muscle soleus were collected from the denervated side and the control side of hind limbs. Total and phosphorylated protein levels of key factors of major signaling pathways in these tissues were determined using western blot assay. Our data showed that total AKT and FoxO3 protein levels were upregulated in denervated muscles as compared with control sides. Phosphorylation of AKT and FoxO3 were proportionally enhanced in denervated EDL but not soleus, indicating AKT activation drives phosphorylation of FoxO3 in EDL but not in soleus upon denervation. As a result, FoxO3‐targeted atrogenes MurF1 and Atrogin1 protein abundances were reduced in denervated EDL but not altered in soleus. In consistent with this change, polyubiquitination were significantly increased in denervated soleus, but only a slight increase in ubiquitination was found in denervated EDL. Autophagy marker LC3 protein level was significantly increased in both muscle types, but in greater extent in EDL after denervation. IRS1 protein level and active ERK were reduced in both muscles upon denervation, which might contribute to the upregulation of total AKT protein level and FoxO3 abundance in EDL and soleus. Total and phosphorylated AMPK protein levels were increased in denervated soleus but not in EDL. Overall, these data reveal that the key signaling pathways that regulate protein synthesis and degradation are more sensitive in soleus than EDL in response to denervation.

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Reduced vagal control of the heart in high-fat diet mice: a potential role of increased butyrylcholinesterase

Cited by 4 publications

References 47 publications

Skeletal muscle secretion of IL-6 is muscle type specific: Ex vivo evidence

Skeletal muscle secretion of IL-6 is muscle type specific: Ex vivo evidence

Interplay Between Systemic Metabolic Cues and Autonomic Output: Connecting Cardiometabolic Function and Parasympathetic Circuits

Distinct signal transductions in fast- and slow- twitch muscles upon denervation

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