Strength exercise reduces hepatic pyruvate carboxylase and gluconeogenesis in DIO mice

Obesity is linked to a reduction in the control of hepatic glucose production, which is the primary mechanism related to fasting hyperglycemia and the development of type 2 diabetes mellitus (T2DM). The main system involved in hepatic gluconeogenesis synthesis is controlled by pyruvate carboxylase (PC), which increases in obesity conditions. Recently, we showed that short-term strength training is an important tool against obesity-induced hyperglycemia. As aerobic exercise can reduce the hepatic PC content of obese animals, we hypothesized that strength exercise can also decrease this gluconeogenic enzyme. Therefore, this study investigated whether the metabolic benefits promoted by short-term strength training are related to changes in hepatic PC content. Swiss mice were divided into three groups: lean control (Ctl), obese sedentary (ObS), and obese short-term strength training (STST). The STST protocol was performed through one session/day for 15 days. The obese exercised animals had reduced hyperglycemia and insulin resistance. These results were related to better control of hepatic glucose production and hepatic insulin sensitivity. Our bioinformatics analysis showed that hepatic PC mRNA levels have positive correlations with glucose levels and adiposity, and negative correlations with locomotor activity and muscle mass. We also found that hepatic mRNA levels are related to lipogenic markers in the liver. Finally, we observed that the obese animals had an increased hepatic PC level; however, STST was efficient in reducing its amount. In conclusion, we provide insights into new biomolecular mechanisms by showing how STST is an efficient tool against obesity-related hyperglycemia and T2DM, even without body weight changes.

Download Full-text

Control of gluconeogenic genes during intense/prolonged exercise: hormone-independent effect of muscle-derived IL-6 on hepatic tissue and PEPCK mRNA

Journal of Applied Physiology ◽

10.1152/japplphysiol.00739.2009 ◽

2009 ◽

Vol 107 (6) ◽

pp. 1830-1839 ◽

Cited By ~ 21

Author(s):

Sébastien Banzet ◽

Nathalie Koulmann ◽

Nadine Simler ◽

Hervé Sanchez ◽

Rachel Chapot ◽

...

Keyword(s):

Phosphoenolpyruvate Carboxykinase ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Independent Effect ◽

Hepatic Tissue ◽

Hepatic Glycogen ◽

Mrna Levels ◽

Hepatic Glucose ◽

Responsive Gene ◽

Gene Mrna

Prolonged intense exercise is challenging for the liver to maintain plasma glucose levels. Hormonal changes cannot fully account for exercise-induced hepatic glucose production (HGP). Contracting skeletal muscles release interleukin-6 (IL-6), a cytokine able to increase endogenous glucose production during exercise. However, whether this is attributable to a direct effect of IL-6 on liver remains unknown. Here, we studied hepatic glycogen, gluconeogenic genes, and IL-6 signaling in response to one bout of exhaustive running exercise in rats. To determine whether IL-6 can modulate gluconeogenic gene mRNA independently of exercise, we injected resting rats with recombinant IL-6. Exhaustive exercise resulted in a profound decrease in liver glycogen and an increase in gluconeogenic gene mRNA levels, phosphoenolpyruvate-carboxykinase (PEPCK), glucose-6-phosphatase (G6P), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), suggesting a key role for gluconeogenesis in hepatic glucose production. This was associated to an active IL-6 signaling in liver tissue, as shown by signal transducer and activator of transcription and CAAT/enhancer binding protein-β phosphorylation and IL-6-responsive gene mRNA levels at the end of exercise. Recombinant IL-6 injection resulted in an increase in IL-6-responsive gene mRNA levels in the liver. We found a dose-dependent increase in PEPCK gene mRNA strongly correlated with IL-6-induced gene mRNA levels. No changes in G6P and PGC-1α mRNA levels were found. Taken together, our results suggest that, during very demanding exercise, muscle-derived IL-6 could help increase HGP by directly upregulating PEPCK mRNA abundance.

Download Full-text

Short-term strength training reduces gluconeogenesis and NAFLD in obese mice

Journal of Endocrinology ◽

10.1530/joe-18-0567 ◽

2019 ◽

Vol 241 (1) ◽

pp. 59-70 ◽

Cited By ~ 8

Author(s):

Rodrigo Martins Pereira ◽

Kellen Cristina da Cruz Rodrigues ◽

Chadi Pellegrini Anaruma ◽

Marcella Ramos Sant’Ana ◽

Thaís Dantis Pereira de Campos ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Strength Training ◽

Term Strength ◽

Obese Mice ◽

Short Term ◽

Fat Accumulation ◽

Hepatic Insulin Sensitivity ◽

Short Term Strength ◽

Hepatic Fat

Non-alcoholic fatty liver disease (NAFLD) has a positive correlation with obesity, insulin resistance and type 2 diabetes mellitus (T2D). The aerobic training is an important tool in combating NAFLD. However, no studies have demonstrated the molecular effects of short-term strength training on the accumulation of hepatic fat in obese mice. This study aimed to investigate the effects of short-term strength training on the mechanisms of oxidation and lipid synthesis in the liver of obese mice. The short duration protocol was used to avoid changing the amount of adipose tissue. Swiss mice were separated into three groups: lean control (CTL), sedentary obese (OB) and strength training obese (STO). The obese groups were fed a high-fat diet (HFD) and the STO group performed the strength training protocol 1 session/day for 15 days. The short-term strength training reduced hepatic fat accumulation, increasing hepatic insulin sensitivity and controlling hepatic glucose production. The obese animals increased the mRNA of lipogenic genes Fasn and Scd1 and reduced the oxidative genes Cpt1a and Ppara. On the other hand, the STO group presented the opposite results. Finally, the obese animals presented higher levels of lipogenic proteins (ACC and FAS) and proinflammatory cytokines (TNF-α and IL-1β), but the short-term strength training was efficient in reducing this condition, regardless of body weight loss. In conclusion, there was a reduction of obesity-related hepatic lipogenesis and inflammation after short-term strength training, independent of weight loss, leading to improvements in hepatic insulin sensitivity and glycemic homeostasis in obese mice. Key points: (1) Short-term strength training (STST) reduced fat accumulation and inflammation in the liver; (2) Hepatic insulin sensitivity and HPG control were increased with STST; (3) The content and activity of ACC and content of FAS were reduced with STST; (4) STST improved hepatic fat accumulation and glycemic homeostasis; (5) STST effects were observed independently of body weight change.

Download Full-text

P684: Neural adaptations following a short-term strength training period: a TMS pilot study

Clinical Neurophysiology ◽

10.1016/s1388-2457(14)50778-x ◽

2014 ◽

Vol 125 ◽

pp. S239

Author(s):

T. Davidson ◽

M. Gerguis ◽

F. Tremblay

Keyword(s):

Pilot Study ◽

Strength Training ◽

Training Period ◽

Term Strength ◽

Short Term ◽

Neural Adaptations ◽

Short Term Strength

Download Full-text

Motor unit synchronization measured by cross-correlation is not influenced by short-term strength training of a hand muscle

Experimental Brain Research ◽

10.1007/s00221-006-0724-z ◽

2006 ◽

Vol 175 (4) ◽

pp. 745-753 ◽

Cited By ~ 19

Author(s):

Dawson J. Kidgell ◽

Martin V. Sale ◽

John G. Semmler

Keyword(s):

Strength Training ◽

Motor Unit ◽

Cross Correlation ◽

Term Strength ◽

Short Term ◽

Short Term Strength ◽

Motor Unit Synchronization ◽

Hand Muscle

Download Full-text

Lack of human muscle architectural adaptation after short-term strength training

Muscle & Nerve ◽

10.1002/mus.20666 ◽

2007 ◽

Vol 35 (1) ◽

pp. 78-86 ◽

Cited By ~ 61

Author(s):

Anthony J. Blazevich ◽

Nicholas D. Gill ◽

Nathan Deans ◽

Shi Zhou

Keyword(s):

Strength Training ◽

Human Muscle ◽

Term Strength ◽

Short Term ◽

Short Term Strength

Download Full-text

Role of hepatic glucose production and glucose uptake in the pathogenesis of fasting hyperglycemia in type 2 diabetes: normalization of glucose kinetics by short-term fasting

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.78.3.536 ◽

1994 ◽

Vol 78 (3) ◽

pp. 536-542 ◽

Cited By ~ 16

Author(s):

F. Fery

Keyword(s):

Type 2 Diabetes ◽

Glucose Uptake ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Glucose Kinetics ◽

Short Term ◽

Hepatic Glucose

Download Full-text

Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00126.2006 ◽

2006 ◽

Vol 291 (3) ◽

pp. E536-E543 ◽

Cited By ~ 21

Author(s):

Chaodong Wu ◽

Salmaan A. Khan ◽

Li-Jen Peng ◽

Honggui Li ◽

Steven G. Carmella ◽

...

Keyword(s):

Insulin Resistance ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Hepatic Insulin Resistance ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Peroxisome Proliferator Activated Receptor ◽

Glucose Flux ◽

Hepatic Glucose

Hepatic insulin resistance is one of the characteristics of type 2 diabetes and contributes to the development of hyperglycemia. How changes in hepatic glucose flux lead to insulin resistance is not clearly defined. We determined the effects of decreasing the levels of hepatic fructose 2,6-bisphosphate (F26P2), a key regulator of glucose metabolism, on hepatic glucose flux in the normal 129J mice. Upon adenoviral overexpression of a kinase activity-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, the enzyme that determines F26P2 level, hepatic F26P2 levels were decreased twofold compared with those of control virus-treated mice in basal state. In addition, under hyperinsulinemic conditions, hepatic F26P2 levels were much lower than those of the control. The decrease in F26P2 leads to the elevation of basal and insulin-suppressed hepatic glucose production. Also, the efficiency of insulin to suppress hepatic glucose production was decreased (63.3 vs. 95.5% suppression of the control). At the molecular level, a decrease in insulin-stimulated Akt phosphorylation was consistent with hepatic insulin resistance. In the low hepatic F26P2 states, increases in both gluconeogenesis and glycogenolysis in the liver are responsible for elevations of hepatic glucose production and thereby contribute to the development of hyperglycemia. Additionally, the increased hepatic gluconeogenesis was associated with the elevated mRNA levels of peroxisome proliferator-activated receptor-γ coactivator-1α and phospho enolpyruvate carboxykinase. This study provides the first in vivo demonstration showing that decreasing hepatic F26P2 levels leads to increased gluconeogenesis in the liver. Taken together, the present study demonstrates that perturbation of glucose flux in the liver plays a predominant role in the development of a diabetic phenotype, as characterized by hepatic insulin resistance.

Download Full-text