Skip to main content
Top
Published in: Sport Sciences for Health 3/2021

01-09-2021 | Insulins | Original Article

Protective effects of HIIT vs. CET exercise training on high-fat-high-fructose diet-induced hyperglycemia, hyperlipidemia, and histopathology of liver in rats: regulation of SIRT1/PGC-1α

Authors: Abolfazl Omidifar, Hossein Shirvani, Ramezan Ali Taheri, Sattar Gorgani-Firouzjae, Maryam Delfan, Fatemeh Kalaki-Jouybari, Soheyla Khakdan

Published in: Sport Sciences for Health | Issue 3/2021

Login to get access

Abstract

Background

Disruption of the function of sirtuin1 (SIRT1) has been reported to link with diabetes and metabolic disorders.

Aim

The aim of this study was to investigate the effect of a modified high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) or continuous endurance training (CET) program on Sirt1 and PGC-1α mRNA gene expression in hepatocytes of high-fat/high-fructose diet-induced diabetes in rats.

Methods

Twenty-eight male Wistar rats (220 ± 20 g) were randomly divided into four groups of non-diabetic (NDC), diabetic control (received high fat high-fructose diet (HFHFD-DC)), CET (HFHFD-CET), and HIIT (HFHFD-HIIT). Diabetes was induced by feeding rats a high-fat (30%) high-fructose (20%) diet for 25 weeks. Following confirmed hyperglycemia, both HFHFD-CET (60–65% Vo2max) and HFHFD-HIIT (85–90% Vo2max) rats underwent treadmill exercise for 30 min, 5 days/week at 10 m/min for 8 weeks. Thereafter, blood and liver samples were obtained for biochemical studies. For histological analysis, the liver was fixed in 10% formalin, embedded in paraffin, and sectioned (5 μm thickness) for H&E staining. SIRT-1 and PGC-1α mRNA expression were measured by RT-PCR from the liver sample (frizzed sample). All data were presented as mean ± standard error mean and compared the differences by one-way analysis of variances. The alpha level was set at 0.05 (p < 0.05) for statistical difference.

Results

The results show that HIIT was more effective than CET to reduce vesicular steatosis. HIIT significantly enhanced the expression of SIRT-1 compared to the HFHFD-DC group (fold change: 1.47, p < 0.047). However, HIIT decreased PGC-1α expression compared to the HFHFD-DC group, but it was not significant (fold change: 1.32 and p < 0.247).

Conclusions

HIIT was more effective than CET in SIRT-1 expression augmentation in high-fat, high-fructose diabetic rats which suggests a possible treatment strategy in the context of type 2 diabetes.
Literature
1.
go back to reference Després J-P, Lemieux I (2006) Abdominal obesity and metabolic syndrome. Nature 444(7121):881–887PubMedCrossRef Després J-P, Lemieux I (2006) Abdominal obesity and metabolic syndrome. Nature 444(7121):881–887PubMedCrossRef
2.
go back to reference AlAmri OD et al (2020) Investigation of antioxidant and anti-inflammatory activities as well as the renal protective potential of green coffee extract in high fat-diet/streptozotocin-induced diabetes in male albino rats. J Funct Foods 71:103996CrossRef AlAmri OD et al (2020) Investigation of antioxidant and anti-inflammatory activities as well as the renal protective potential of green coffee extract in high fat-diet/streptozotocin-induced diabetes in male albino rats. J Funct Foods 71:103996CrossRef
3.
4.
go back to reference Samuel VT (2011) Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab 22(2):60–65PubMedCrossRef Samuel VT (2011) Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab 22(2):60–65PubMedCrossRef
6.
go back to reference Feng W et al (2020) Effects of astaxanthin on inflammation and insulin resistance in a mouse model of gestational diabetes mellitus. Dose Response 18(2):1559325820926765PubMedPubMedCentralCrossRef Feng W et al (2020) Effects of astaxanthin on inflammation and insulin resistance in a mouse model of gestational diabetes mellitus. Dose Response 18(2):1559325820926765PubMedPubMedCentralCrossRef
7.
go back to reference Alberti KGM, Zimmet P, Shaw J (2005) The metabolic syndrome—a new worldwide definition. Lancet 366(9491):1059–1062PubMedCrossRef Alberti KGM, Zimmet P, Shaw J (2005) The metabolic syndrome—a new worldwide definition. Lancet 366(9491):1059–1062PubMedCrossRef
8.
go back to reference Kalaki-Jouybari F et al (2018) High-intensity interval training (HIIT) alleviated NAFLD feature via miR-122 induction in liver of high-fat high-fructose diet induced diabetic rats. Archiv Physiol Biochem 1–8 Kalaki-Jouybari F et al (2018) High-intensity interval training (HIIT) alleviated NAFLD feature via miR-122 induction in liver of high-fat high-fructose diet induced diabetic rats. Archiv Physiol Biochem 1–8
9.
go back to reference Omidifar A et al (2019) The gene expression of CTRP12 but not CTRP13 is upregulated in both visceral and subcutaneous adipose tissue of obese subjects. Diabetes Metab Syndrome Clin Res Rev 13(4):2593–2599CrossRef Omidifar A et al (2019) The gene expression of CTRP12 but not CTRP13 is upregulated in both visceral and subcutaneous adipose tissue of obese subjects. Diabetes Metab Syndrome Clin Res Rev 13(4):2593–2599CrossRef
10.
go back to reference Purushotham A et al (2009) Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 9(4):327–338PubMedPubMedCentralCrossRef Purushotham A et al (2009) Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 9(4):327–338PubMedPubMedCentralCrossRef
11.
go back to reference Chang H-C, Guarente L (2014) SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab 25(3):138–145PubMedCrossRef Chang H-C, Guarente L (2014) SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab 25(3):138–145PubMedCrossRef
13.
go back to reference Rodgers JT et al (2005) Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature 434(7029):113PubMedCrossRef Rodgers JT et al (2005) Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature 434(7029):113PubMedCrossRef
14.
go back to reference Lagouge M et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 127(6):1109–1122PubMedCrossRef Lagouge M et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 127(6):1109–1122PubMedCrossRef
15.
go back to reference Sobhani V et al (2018) High-intensity interval training-induced inflammation and airway narrowing of the lung parenchyma in male maturing rats. Comp Clin Pathol 27(3):577–582CrossRef Sobhani V et al (2018) High-intensity interval training-induced inflammation and airway narrowing of the lung parenchyma in male maturing rats. Comp Clin Pathol 27(3):577–582CrossRef
16.
go back to reference Arabzadeh E, Mirdar S, Moradiani H (2016) Nigella sativa supplementation attenuates exercise-induced bronchoconstriction in the maturing rat: a histometric and histologic study. Comp Clin Pathol 25(1):1–5CrossRef Arabzadeh E, Mirdar S, Moradiani H (2016) Nigella sativa supplementation attenuates exercise-induced bronchoconstriction in the maturing rat: a histometric and histologic study. Comp Clin Pathol 25(1):1–5CrossRef
17.
go back to reference Arabzadeh E, Mirdar S, Fathi Z (2015) Measurement of levels of lung HIF-1α protein in response to tapering for 14-and 21-day with nigella sativa supplementation in maturing rat, with histological study. Sport Sci Health 11(2):195–202CrossRef Arabzadeh E, Mirdar S, Fathi Z (2015) Measurement of levels of lung HIF-1α protein in response to tapering for 14-and 21-day with nigella sativa supplementation in maturing rat, with histological study. Sport Sci Health 11(2):195–202CrossRef
18.
go back to reference Huang C-C et al (2016) Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. Int J Med Sci 13(4):260PubMedPubMedCentralCrossRef Huang C-C et al (2016) Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. Int J Med Sci 13(4):260PubMedPubMedCentralCrossRef
19.
go back to reference De Angelis K et al (2002) Cardiovascular control in experimental diabetes. Braz J Med Biol Res 35:1091–1100PubMedCrossRef De Angelis K et al (2002) Cardiovascular control in experimental diabetes. Braz J Med Biol Res 35:1091–1100PubMedCrossRef
20.
go back to reference Holloway TM et al (2015) High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats. PLoS ONE 10(3):e0121138PubMedPubMedCentralCrossRef Holloway TM et al (2015) High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats. PLoS ONE 10(3):e0121138PubMedPubMedCentralCrossRef
21.
go back to reference Finucane F et al (2010) The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial. Diabetologia 53(4):624–631PubMedCrossRef Finucane F et al (2010) The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial. Diabetologia 53(4):624–631PubMedCrossRef
22.
23.
go back to reference Tsekouras YE et al (2008) High-intensity interval aerobic training reduces hepatic very low-density lipoprotein-triglyceride secretion rate in men. Am J Physiol Endocrinol Metab 295(4):E851–E858PubMedCrossRef Tsekouras YE et al (2008) High-intensity interval aerobic training reduces hepatic very low-density lipoprotein-triglyceride secretion rate in men. Am J Physiol Endocrinol Metab 295(4):E851–E858PubMedCrossRef
24.
go back to reference Kauppinen A et al (2013) Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 25(10):1939–1948PubMedCrossRef Kauppinen A et al (2013) Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 25(10):1939–1948PubMedCrossRef
25.
go back to reference Sampey BP et al (2011) Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity 19(6):1109–1117PubMedCrossRef Sampey BP et al (2011) Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity 19(6):1109–1117PubMedCrossRef
26.
go back to reference Axelsen LN et al (2010) Metabolic and cardiac changes in high cholesterol–fructose-fed rats. J Pharmacol Toxicol Methods 61(3):292–296PubMedCrossRef Axelsen LN et al (2010) Metabolic and cardiac changes in high cholesterol–fructose-fed rats. J Pharmacol Toxicol Methods 61(3):292–296PubMedCrossRef
27.
go back to reference Chavanelle V et al (2017) Effects of high-intensity interval training and moderate-intensity continuous training on glycaemic control and skeletal muscle mitochondrial function in db/db mice. Sci Rep 7(1):1–10CrossRef Chavanelle V et al (2017) Effects of high-intensity interval training and moderate-intensity continuous training on glycaemic control and skeletal muscle mitochondrial function in db/db mice. Sci Rep 7(1):1–10CrossRef
28.
go back to reference Ghareghani P et al (2018) Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice. Obesity Res Clin Practice 12(1):80–89CrossRef Ghareghani P et al (2018) Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice. Obesity Res Clin Practice 12(1):80–89CrossRef
29.
go back to reference Cassidy S et al (2017) High-intensity interval training: a review of its impact on glucose control and cardiometabolic health. Diabetologia 60(1):7–23PubMedCrossRef Cassidy S et al (2017) High-intensity interval training: a review of its impact on glucose control and cardiometabolic health. Diabetologia 60(1):7–23PubMedCrossRef
30.
go back to reference Majid H, Masood Q, Khan AH (2017) Homeostatic model assessment for insulin resistance (HOMA-IR): a better marker for evaluating insulin resistance than fasting insulin in women with polycystic ovarian syndrome. J Coll Physicians Surg Pak 27(3):123–126PubMed Majid H, Masood Q, Khan AH (2017) Homeostatic model assessment for insulin resistance (HOMA-IR): a better marker for evaluating insulin resistance than fasting insulin in women with polycystic ovarian syndrome. J Coll Physicians Surg Pak 27(3):123–126PubMed
31.
go back to reference Liu H-W, Kao H-H, Wu C-H (2019) Exercise training upregulates SIRT1 to attenuate inflammation and metabolic dysfunction in kidney and liver of diabetic db/db mice. Nutr Metab 16(1):22CrossRef Liu H-W, Kao H-H, Wu C-H (2019) Exercise training upregulates SIRT1 to attenuate inflammation and metabolic dysfunction in kidney and liver of diabetic db/db mice. Nutr Metab 16(1):22CrossRef
32.
go back to reference De Nardi AT et al (2018) High-intensity interval training versus continuous training on physiological and metabolic variables in prediabetes and type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract 137:149–159PubMedCrossRef De Nardi AT et al (2018) High-intensity interval training versus continuous training on physiological and metabolic variables in prediabetes and type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract 137:149–159PubMedCrossRef
33.
go back to reference Winding KM et al (2018) The effect on glycaemic control of low-volume high-intensity interval training versus endurance training in individuals with type 2 diabetes. Diabetes Obes Metab 20(5):1131–1139PubMedCrossRef Winding KM et al (2018) The effect on glycaemic control of low-volume high-intensity interval training versus endurance training in individuals with type 2 diabetes. Diabetes Obes Metab 20(5):1131–1139PubMedCrossRef
34.
go back to reference Boutant M, Cantó C (2014) SIRT1 metabolic actions: Integrating recent advances from mouse models. Mol Metab 3(1):5–18PubMedCrossRef Boutant M, Cantó C (2014) SIRT1 metabolic actions: Integrating recent advances from mouse models. Mol Metab 3(1):5–18PubMedCrossRef
36.
go back to reference Stefanowicz M et al (2018) Adipose tissue, but not skeletal muscle, sirtuin 1 expression is decreased in obesity and related to insulin sensitivity. Endocrine 60(2):263–271PubMedPubMedCentralCrossRef Stefanowicz M et al (2018) Adipose tissue, but not skeletal muscle, sirtuin 1 expression is decreased in obesity and related to insulin sensitivity. Endocrine 60(2):263–271PubMedPubMedCentralCrossRef
37.
go back to reference Li Y et al (2011) Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J 25(5):1664–1679PubMedPubMedCentralCrossRef Li Y et al (2011) Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J 25(5):1664–1679PubMedPubMedCentralCrossRef
39.
go back to reference Colberg SR et al (2010) Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care 33(12):e147–e167PubMedPubMedCentralCrossRef Colberg SR et al (2010) Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care 33(12):e147–e167PubMedPubMedCentralCrossRef
40.
go back to reference de Lade CG et al (2018) Effects of moderate intensity endurance training vs high intensity interval training on weight gain, cardiorespiratory capacity, and metabolic profile in postnatal overfed rats. Diabetol Metab Syndrome 10(1):70CrossRef de Lade CG et al (2018) Effects of moderate intensity endurance training vs high intensity interval training on weight gain, cardiorespiratory capacity, and metabolic profile in postnatal overfed rats. Diabetol Metab Syndrome 10(1):70CrossRef
41.
go back to reference Holloway TM et al (2015) High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension. Am J Physiol Regul Integr Comp Physiol 308(11):R927–R934PubMedCrossRef Holloway TM et al (2015) High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension. Am J Physiol Regul Integr Comp Physiol 308(11):R927–R934PubMedCrossRef
42.
go back to reference Oliveira NRC et al (2014) Treadmill training increases SIRT-1 and PGC-1α protein levels and AMPK phosphorylation in quadriceps of middle-aged rats in an intensity-dependent manner. Mediators Inflamm 2014:11CrossRef Oliveira NRC et al (2014) Treadmill training increases SIRT-1 and PGC-1α protein levels and AMPK phosphorylation in quadriceps of middle-aged rats in an intensity-dependent manner. Mediators Inflamm 2014:11CrossRef
43.
go back to reference Bayod S et al (2012) Long-term physical exercise induces changes in sirtuin 1 pathway and oxidative parameters in adult rat tissues. Exp Gerontol 47(12):925–935PubMedCrossRef Bayod S et al (2012) Long-term physical exercise induces changes in sirtuin 1 pathway and oxidative parameters in adult rat tissues. Exp Gerontol 47(12):925–935PubMedCrossRef
44.
go back to reference Moreno-Santos I et al (2016) Type 2 diabetes is associated with decreased PGC1α expression in epicardial adipose tissue of patients with coronary artery disease. J Transl Med 14(1):243–243PubMedPubMedCentralCrossRef Moreno-Santos I et al (2016) Type 2 diabetes is associated with decreased PGC1α expression in epicardial adipose tissue of patients with coronary artery disease. J Transl Med 14(1):243–243PubMedPubMedCentralCrossRef
45.
go back to reference Besse-Patin A et al (2019) PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin. Proc Natl Acad Sci 116(10):4285PubMedPubMedCentralCrossRef Besse-Patin A et al (2019) PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin. Proc Natl Acad Sci 116(10):4285PubMedPubMedCentralCrossRef
46.
Metadata
Title
Protective effects of HIIT vs. CET exercise training on high-fat-high-fructose diet-induced hyperglycemia, hyperlipidemia, and histopathology of liver in rats: regulation of SIRT1/PGC-1α
Authors
Abolfazl Omidifar
Hossein Shirvani
Ramezan Ali Taheri
Sattar Gorgani-Firouzjae
Maryam Delfan
Fatemeh Kalaki-Jouybari
Soheyla Khakdan
Publication date
01-09-2021
Publisher
Springer Milan
Published in
Sport Sciences for Health / Issue 3/2021
Print ISSN: 1824-7490
Electronic ISSN: 1825-1234
DOI
https://doi.org/10.1007/s11332-021-00736-9

Other articles of this Issue 3/2021

Sport Sciences for Health 3/2021 Go to the issue