Intracranial administration of transforming growth factor-β3 increases fat oxidation in rats

2002 ◽  
Vol 283 (3) ◽  
pp. E536-E544 ◽  
Author(s):  
Hanae Yamazaki ◽  
Masanao Arai ◽  
Shigenobu Matsumura ◽  
Kazuo Inoue ◽  
Tohru Fushiki
Keyword(s):  
Growth Factor ◽  
Energy Expenditure ◽  
Motor Activity ◽  
Transforming Growth Factor ◽  
Ketone Bodies ◽  
Fat Oxidation ◽  
Spontaneous Motor Activity ◽  
Total Carbohydrate ◽  
Intracranial Injection ◽  
Total Fat

The effects of intracranial transforming growth factor (TGF)-β3 on spontaneous motor activity and energy metabolism were examined in rats. After injection of TGF-β3 into the cisterna magna of the rat, spontaneous motor activity decreased significantly for 1 h. The intracranial injection of TGF-β3 produced an immediate decrease in respiratory exchange ratio (RER). No significant changes were observed in energy expenditure. TGF-β3 induced a significant increase in total fat oxidation and a decrease in total carbohydrate oxidation. Furthermore, the serum substrates associated with fat metabolism were significantly altered in rats injected with TGF-β3. Both lipoprotein lipase activity in skeletal muscle and the concentration of serum ketone bodies increased, suggesting that the increase in fat oxidation caused by TGF-β3 may have occurred in the liver and muscle. Intracranial injection of TGF-β3 appeared to evoke a switch in the energy substrates accessed in energy expenditure. These results suggest that the release of TGF-β3 in the brain by exercise is a signal for regulating energy consumption.

scholarly journals Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2580
Author(s):  
Won Kil Lee ◽  
Yeongyeong Kim ◽  
Heejin Jang ◽  
Joo Hye Sim ◽  
Hye Jin Choi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Neuroblastoma Cell ◽  
Critical Role ◽  
Central Fatigue ◽  
Chronic Fatigue ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Intracranial Injection ◽  
Tgf Β1

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is one of the most refractory diseases in humans and is characterized by severe central fatigue accompanied with various symptoms that affect daily life, such as impaired memory, depression, and somatic pain. However, the etiology and pathophysiological mechanisms of CFS remain unknown. To investigate the pathophysiological role of transforming growth factor (TGF)-β1, we injected a cytokine into the lateral ventricle of a C57BL/6 mouse. The intracranial injection of TGF-β1 increased the immobility duration in a forced swimming test (FST) and time spent at the closed arm in elevated plus maze (EPM) analysis. The mice injected with TGF-β1 into their brain showed increased sensitivity to pain in a von Frey test, and had a decreased retention time on rotarod and latency time in a bright box in a passive avoidance test. In addition, the serum levels of muscle fatigue biomarkers, lactate dehydrogenase (LDH) and creatine kinase (CK), were significantly increased after administration of TGF-β1. Intracranial injection of TGF-β1 significantly reduced the production of tyrosine hydroxylase (TH) in the ventral tegmental area, accompanied by a decreased level of dopamine in the striatum. The suppression of TH expression by TGF-β1 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-β1 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-β1 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease.

Transforming growth factor-β in the brain is activated by exercise and increases mobilization of fat-related energy substrates in rats

2007 ◽  
Vol 292 (5) ◽  
pp. R1851-R1861 ◽  
Author(s):  
Tetsuro Shibakusa ◽  
Wataru Mizunoya ◽  
Yuki Okabe ◽  
Shigenobu Matsumura ◽  
Yoko Iwaki ◽  
...  
Keyword(s):  
Nervous System ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Ketone Bodies ◽  
Nonesterified Fatty Acid ◽  
Energy Substrates ◽  
Low Intensity ◽  
Related Energy ◽  
Low Intensity Exercise ◽  
The Brain

We have recently reported that inhibition of transforming growth factor (TGF)-β in the brain reduced fat-related energy substrates concentrations in response to exercise. We investigated the relevance between the mobilization of fat-related energy substrates (nonesterified fatty acid and ketone bodies) during exercise and the effects of TGF-β in the brain. Low-intensity exercise was simulated by contraction of the hindlimbs, induced by electrical stimulation at 2 Hz in anesthetized rats (Sim-Ex). As with actual exercise, it was confirmed that mobilization of carbohydrate-related energy substrates (glucose and lactic acid) occurred immediately after the onset of Sim-Ex, and mobilization of fat-related energy substrates followed thereafter. The timing of mobilization of fat-related substrates corresponded to that of the increase in TGF-β in cerebrospinal fluid (CSF) in Sim-Ex. The level of TGF-β in CSF significantly increased after 10 min of Sim-Ex and remained elevated until 30 min of Sim-Ex. Intracisternal administration of TGF-β caused rapid mobilization of fat-related energy substrates. Meanwhile, there were no effects on the changes in carbohydrate-related substrates. The levels of catecholamines were slightly elevated after TGF-β administration, and, although not significantly in statistical terms, we consider that at least a part of TGF-β signal was transducted via the sympathetic nervous system because of these increases. These data indicate that TGF-β in the brain is closely related to the mobilization of fat-related energy substrates during low-intensity exercise. We hypothesized that the central nervous system plays a role in the regulation of energy metabolism during low-intensity exercise and this may be mediated by TGF-β.

scholarly journals Glucose kinetics and substrate oxidation during exercise in the follicular and luteal phases

2001 ◽  
Vol 90 (2) ◽  
pp. 447-453 ◽  
Author(s):  
Ted W. Zderic ◽  
Andrew R. Coggan ◽  
Brent C. Ruby
Keyword(s):  
Plasma Glucose ◽  
Lactate Concentration ◽  
Fat Oxidation ◽  
Substrate Oxidation ◽  
Constant Infusion ◽  
Moderate Intensity ◽  
Glucose Kinetics ◽  
Moderate Intensity Exercise ◽  
Total Carbohydrate ◽  
Total Fat

The purpose of this investigation was to determine whether plasma glucose kinetics and substrate oxidation during exercise are dependent on the phase of the menstrual cycle. Once during the follicular (F) and luteal (L) phases, moderately trained subjects [peak O2 uptake (V˙o 2) = 48.2 ± 1.1 ml · min−1 · kg−1; n = 6] cycled for 25 min at ∼70% of theV˙o 2 at their respective lactate threshold (70%LT), followed immediately by 25 min at 90%LT. Rates of plasma glucose appearance (Ra) and disappearance (Rd) were determined with a primed constant infusion of [6,6-2H]glucose, and total carbohydrate (CHO) and fat oxidation were determined with indirect calorimetry. At rest and during exercise at 70%LT, there were no differences in glucose Raor Rd between phases. CHO and fat oxidation were not different between phases at 70%LT. At 90%LT, glucose Ra(28.8 ± 4.8 vs. 33.7 ± 4.5 μmol · min−1 · kg−1; P < 0.05) and Rd (28.4 ± 4.8 vs. 34.0 ± 4.1 μmol · min−1 · kg−1; P < 0.05) were lower during the L phase. In addition, at 90%LT, CHO oxidation was lower during the L compared with the F phase (82.0 ± 12.3 vs. 93.8 ± 9.7 μmol · min−1 · kg−1; P < 0.05). Conversely, total fat oxidation was greater during the L phase at 90%LT (7.46 ± 1.01 vs. 6.05 ± 0.89 μmol · min−1 · kg−1; P < 0.05). Plasma lactate concentration was also lower during the L phase at 90%LT concentrations (2.48 ± 0.41 vs. 3.08 ± 0.39 mmol/l; P < 0.05). The lower CHO utilization during the L phase was associated with an elevated resting estradiol ( P < 0.05). These results indicate that plasma glucose kinetics and CHO oxidation during moderate-intensity exercise are lower during the L compared with the F phase in women. These differences may have been due to differences in circulating estradiol.

scholarly journals Ketogenic Diet Enhances the Cholesterol Accumulation in Liver and Augments the Severity of CCl4 and TAA-Induced Liver Fibrosis in Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 2934
Author(s):  
Yi-Jen Liao ◽  
Yuan-Hsi Wang ◽  
Chien-Ying Wu ◽  
Fang-Yu Hsu ◽  
Chia-Ying Chien ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Ketogenic Diet ◽  
Transforming Growth Factor ◽  
Ketone Bodies ◽  
Stellate Cell ◽  
Metabolic Effects ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Fibrosis Progression

Persistent chronic liver diseases increase the scar formation and extracellular matrix accumulation that further progress to liver fibrosis and cirrhosis. Nevertheless, there is no antifibrotic therapy to date. The ketogenic diet is composed of high fat, moderate to low-protein, and very low carbohydrate content. It is mainly used in epilepsy and Alzheimer’s disease. However, the effects of the ketogenic diet on liver fibrosis remains unknown. Through ketogenic diet consumption, β-hydroxybutyrate (bHB) and acetoacetate (AcAc) are two ketone bodies that are mainly produced in the liver. It is reported that bHB and AcAc treatment decreases cancer cell proliferation and promotes apoptosis. However, the influence of bHB and AcAc in hepatic stellate cell (HSC) activation and liver fibrosis are still unclear. Therefore, this study aimed to investigate the effect of the ketogenic diet and ketone bodies in affecting liver fibrosis progression. Our study revealed that feeding a high-fat ketogenic diet increased cholesterol accumulation in the liver, which further enhanced the carbon tetrachloride (CCl4)- and thioacetamide (TAA)-induced liver fibrosis. In addition, more severe liver inflammation and the loss of hepatic antioxidant and detoxification ability were also found in ketogenic diet-fed fibrotic mouse groups. However, the treatment with ketone bodies (bHB and AcAc) did not suppress transforming growth factor-β (TGF-β)-induced HSC activation, platelet-derived growth factor (PDGF)-BB-triggered proliferation, and the severity of CCl4-induced liver fibrosis in mice. In conclusion, our study demonstrated that feeding a high-fat ketogenic diet may trigger severe steatohepatitis and thereby promote liver fibrosis progression. Since a different ketogenic diet composition may exert different metabolic effects, more evidence is necessary to clarify the effects of a ketogenic diet on disease treatment.

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