Research Progress on the effect of High altitude and hypoxia on Mitochondrial function in Obesity

  • Ying Liu Shaanxi University of Chinese Medicine
  • Baoning Qi Shaanxi University of Chinese Medicine
  • Wenbin Zhang Military Medical University of the Air Force
  • Yifan Zhang Fourth Military Medical University
  • Wenqing Wei Shaanxi University of Chinese Medicine
Keywords: High Altitude; Hypoxia; Obesity; Insulin; Skeletal Muscle; Mitochondrial Metabolism


Obesity is one of the diseases that threaten human health at present, and it can lead to the increasing prevalence of related complications, such as Insulin resistance, Non-alcoholic fatty liver diseases NAFLD and Type 2 diabetes mellitus and so on. In the whole world, the prevalence rate of obesity is on the rise. Insulin resistance is one of the most common complications of obesity. More and more studies have shown that there is a close relationship between mitochondrial dysfunction and insulin resistance. Skeletal muscle is an important target organ of insulin. Skeletal muscle mitochondrial dysfunction can lead to abnormal glucose and lipid metabolism and further affect the signal pathway of energy metabolism. The new epidemiological survey shows that the prevalence of obesity in high altitude areas is significantly lower than that in plain areas, and the prevalence of overweight and obesity is negatively correlated with altitude. This paper discusses the relationship between high altitude hypoxia and mitochondrial metabolism.


[1] Chandler M, Cunningham S, Lund E M, et al. Obesity and Associated Comorbidities in People and Companion Animals: A One

Health Perspective[J]. J Comp Pathol, 2017, 156(4): 296-309.

[2] Saltiel A R, Olefsky J M. Inflammatory mechanisms linking obesity and metabolic disease[J]. J Clin Invest, 2017, 127(1): 1-4.

[3] Rahtu-Korpela L, Karsikas S, Horkko S, et al. HIF prolyl 4-hydroxylase2 inhibition improves glucose and lipid metabolism and

protects against obesity and metabolic dysfunction[J]. Diabetes, 2014, 63(10): 3324-33.

[4] Crichton G E, Alkerwi A. Physical activity, sedentary behavior time and lipid levels in the Observation of Cardiovascular Risk

Factors in Luxembourg study[J]. Lipids Health Dis, 2015, 14: 87.

[5] Jezewska-Zychowicz M, Gebski J, Guzek D, et al. The Associations between Dietary Patterns and Sedentary Behaviors in Polish

Adults (LifeStyle Study) [J]. Nutrients, 2018, 10(8)

[6] Sherpa L Y, Deji, Stigum H, et al. Obesity in Tibetans aged 30-70 living at different altitudes under the north and south faces of Mt.

Everest[J]. Int J Environ Res Public Health, 2010, 7(4): 1670-80.

[7] Lippl F J, Neubauer S, Schipfer S, et al. Hypobaric hypoxia causes body weight reduction in obese subjects[J]. Obesity (Silver

Spring), 2010, 18(4): 675-81.

[8] Molnar D, Schutz Y. The effect of obesity, age, puberty and gender on resting metabolic rate in children and adolescents[J]. Eur J

Pediatr, 1997, 156(5): 376-81.

[9] Meex R C R, Watt M J. Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance[J]. Nat Rev Endocrinol, 2017,

13(9): 509-520.

[10] Zhao R R, O’Sullivan A J, Fiatarone Singh M A. Exercise or physical activity and cognitive function in adults with type 2 diabetes, insulin resistance or impaired glucose tolerance: a systematic review[J]. Eur Rev Aging Phys Act, 2018, 15: 1.

[11] NE H, K D, J M, et al. Continuous Glucose Monitoring at High Altitude-Effects on Glucose Homeostasis[J]. Medicine and science in sports and exercise, 2018, 50(8): 1679-1686.

[12] Aryal N, Weatherall M, Bhatta Y K D, et al. Lipid Profiles, Glycated Hemoglobin, and Diabetes in People Living at High Altitude

in Nepal[J]. Int J Environ Res Public Health, 2017, 14(9)

[13] Woolcott O O, Ader M, Bergman R N. Glucose homeostasis during short-term and prolonged exposure to high altitudes[J]. Endo_x005fcr Rev, 2015, 36(2): 149-73.

[14] Holden J E, Stone C K, Clark C M, et al. Enhanced cardiac metabolism of plasma glucose in high-altitude natives: adaptation

against chronic hypoxia[J]. J Appl Physiol (1985), 1995, 79(1): 222-8.

[15] Castillo O, Woolcott O O, Gonzales E, et al. Residents at high altitude show a lower glucose profile than sea-level residents

throughout 12-hour blood continuous monitoring[J]. High Alt Med Biol, 2007, 8(4): 307-11

[16] Putti R, Migliaccio V, Sica R, et al. Skeletal Muscle Mitochondrial Bioenergetics and Morphology in High Fat Diet Induced Obesity and Insulin Resistance: Focus on Dietary Fat Source[J]. Front Physiol, 2015, 6: 426.

[17] Lark D S, Fisher-Wellman K H, Neufer P D. High-fat load: mechanism(s) of insulin resistance in skeletal muscle[J]. Int J Obes

Suppl, 2012, 2(Suppl 2): S31-S36

[18] Crossland H, Skirrow S, Puthucheary Z A, et al. The impact of immobilisation and inflammation on the regulation of muscle mass

and insulin resistance: different routes to similar end-points[J]. J Physiol, 2019, 597(5): 1259-1270.

[19] Perez-Schindler J, Philp A. Regulation of skeletal muscle mitochondrial function by nuclear receptors: implications for health and

disease[J]. Clin Sci (Lond), 2015, 129(7): 589-99.

[20] Montgomery M K, Turner N. Mitochondrial dysfunction and insulin resistance: an update[J]. Endocr Connect, 2015, 4(1): R1-


[21] Garcia-Roves P M. Mitochondrial pathophysiology and type 2 diabetes mellitus[J]. Arch Physiol Biochem, 2011, 117(3): 177-87.

[22] Lewis M T, Kasper J D, Bazil J N, et al. Quantification of Mitochondrial Oxidative Phosphorylation in Metabolic Disease: Application to Type 2 Diabetes[J]. Int J Mol Sci, 2019, 20(21)

[23] Rovira-Llopis S, Banuls C, Diaz-Morales N, et al. Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications[J].

Redox Biol, 2017, 11: 637-645.

[24] Varga N A, Pentelenyi K, Balicza P, et al. Mitochondrial dysfunction and autism: comprehensive genetic analyses of children with

autism and mtDNA deletion[J]. Behav Brain Funct, 2018, 14(1): 4.

[25] Parish R, Petersen K F. Mitochondrial dysfunction and type 2 diabetes[J]. Curr Diab Rep, 2005, 5(3): 177-83.

[26] Civitarese A E, Ravussin E. Mitochondrial energetics and insulin resistance[J]. Endocrinology, 2008, 149(3): 950-4.

[27] Herzig S, Shaw R J. AMPK: guardian of metabolism and mitochondrial homeostasis[J]. Nat Rev Mol Cell Biol, 2018, 19(2): 121-


[28] Lantier L, Fentz J, Mounier R, et al. AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle

integrity[J]. FASEB J, 2014, 28(7): 3211-24.

[29] Kelly D P, Scarpulla R C. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function[J]. Genes Dev,

2004, 18(4): 357-68.

[30] Ekstrand M I, Falkenberg M, Rantanen A, et al. Mitochondrial transcription factor A regulates mtDNA copy number in mammals[J]. Hum Mol Genet, 2004, 13(9): 935-44.

Review Article