TIGAR deficiency enhances skeletal muscle thermogenesis by increasing neuromuscular junction cholinergic signaling

Tang, Yan; Zong, Haihong; Kwon, Hyokjoon; Qiu, Yunping; Pessin, Jacob B.; Wu, Licheng; Buddo, Katherine A; Boykov, Ilya; Schmidt, Cameron A.; Lin, Chien-Te; Neufer, P. Darrell; Schwartz, Gary J.; Kurland, Irwin J.; Pessin, Jeffrey E.

doi:10.7554/elife.73360

Cited by 2 publications

(4 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sympathetic nervous system (SNS) releases NE, DA, and acetylcholine (ACh) at effector organlevels, affecting smooth muscles, the heart, and glands [43] . Noradrenaline predominantly stimulates alpha-adrenergic receptors (α1-ARs, α2-ARs), while E predominantly activates beta-adrenergic receptors (β1-ARs, β2-ARs, β3-ARs) [43] .…”

Section: Discussionmentioning

confidence: 99%

“…Cholinergic pathways (from the sacral region of the spinal cord) play a crucial role in the shivering response to cold exposure (ACh-mediated skeletal muscle tremors via stimulation of nicotinic receptors). Shivering generates heat, helping to maintain body temperature, regardless of an individual’s physical condition [43] .…”

Section: Discussionmentioning

confidence: 99%

“…The adrenal medulla releases catecholamines like epinephrine (E), norepinephrine (NE), and dopamine (DA) (8,11,(19)(20)(21)(38)(39)(40)(41)(42). The sympathetic nervous system (SNS) releases NE, DA, and acetylcholine (ACh) at effector organ levels, affecting smooth muscles, the heart, and glands (43). Noradrenaline predominantly stimulates alpha-adrenergic receptors (a1-ARs, a2-ARs), while E predominantly activates beta-adrenergic receptors (b1-ARs, b2-ARs, b3-ARs) (43).…”

Section: Stimulation Of Adrenergic and Cholinergic Pathwaysmentioning

confidence: 99%

See 2 more Smart Citations

Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches

et al. 2024

View full text Add to dashboard Cite

Background: The extent to which homeostatically regulated physiological processes (including cardiorespiratory fitness expressed as VO2max) are involved in response to physical stressors (which include acclimatization and marching) has not been studied,, and we intended to make this assessment based on measured cortisol levels and blood lactate in subjects exposed to summer and winter acclimatization and marching. Methods: Two groups of young men with poor (PCF; n=9) and better physical condition (GCF; n=21), corresponding to the VO2max threshold of 40mL O2/kg/min, marched 15 km at an average speed of 6-7 km/h, in winter (5˚C) and in summer (32˚C). Blood sampling was performed in the morning hours (10 am) before and immediately after the march. At the same time, the participants' pulses had not yet settled, and cortisol and lactate analyses were performed using routine methods. Results: Basal cortisol was significantly elevated at 5°C in the PCF group. After marching, cortisol decreased substantially in both groups at 5°C. Basal and post-marching cortisol levels were significantly elevated only at 32°C in the GCF group. Conclusions: Cold is more stressful to the body than heat and physical activity reduces cold-related stress, regardless of fitness. Individuals with poorer fitness are more susceptible to cold or heat stress. Only individuals with better physical fitness (associated with lower cortisol levels) had higher lactate levels at baseline and after marching at 32 °C, confirming that their energy metabolism is more dependent on lactate metabolism and that they are less stressed under these conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Stimulation Of Adrenergic and Cholinergic Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches

et al. 2024

View full text Add to dashboard Cite

show abstract

“…These findings demonstrate that functional gluconeogenic activity can significantly increase in pericentral hepatocytes after prolonged food deprivation but remains higher in the periportal hepatocytes compared to the pericentral hepatocytes. A key decision point for whether substrate flux goes towards de novo lipogenesis or gluconeogenesis is the conversion of pyruvate to either acetyl CoA by pyruvate dehydrogenase (PDH) or to oxaloacetate by pyruvate decarboxylase (PC) 38,39,40,41 .…”

Section: Gluconeogenic Activity In Isolated Primary Periportal and Pe...mentioning

confidence: 99%

Spatial hepatocyte plasticity of gluconeogenesis during the metabolic transitions between fed, fasted and starvation states

Okada,

Landgraf,

Xiaoli

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The liver acts as a master regulator of metabolic homeostasis in part by performing gluconeogenesis. This process is dysregulated in type 2 diabetes, leading to elevated hepatic glucose output. The parenchymal cells of the liver (hepatocytes) are heterogeneous, existing on an axis between the portal triad and the central vein, and perform distinct functions depending on location in the lobule. Here, using single cell analysis of hepatocytes across the liver lobule, we demonstrate that gluconeogenic gene expression (Pck1 and G6pc) is relatively low in the fed state and gradually increases first in the periportal hepatocytes during the initial fasting period. As the time of fasting progresses, pericentral hepatocyte gluconeogenic gene expression increases, and following entry into the starvation state, the pericentral hepatocytes show similar gluconeogenic gene expression to the periportal hepatocytes. Similarly, pyruvate-dependent gluconeogenic activity is approximately 10-fold higher in the periportal hepatocytes during the initial fasting state but only 1.5-fold higher in the starvation state. In parallel, starvation suppresses canonical beta-catenin signaling and modulates expression of pericentral and periportal glutamine synthetase and glutaminase, resulting in an enhanced pericentral glutamine-dependent gluconeogenesis. These findings demonstrate that hepatocyte gluconeogenic gene expression and gluconeogenic activity are highly spatially and temporally plastic across the liver lobule, underscoring the critical importance of using well-defined feeding and fasting conditions to define the basis of hepatic insulin resistance and glucose production.

show abstract

TIGAR deficiency enhances skeletal muscle thermogenesis by increasing neuromuscular junction cholinergic signaling

Cited by 2 publications

References 60 publications

Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches

Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches

Spatial hepatocyte plasticity of gluconeogenesis during the metabolic transitions between fed, fasted and starvation states

Contact Info

Product

Resources

About