Appetite Control with Relevance to Mitochondrial Biogenesis and Activation of Post-Prandial Lipid Metabolism in Obesity Linked Diabetes


Ann Obes Disord. 2016; 1(3): 1012.

Appetite Control with Relevance to Mitochondrial Biogenesis and Activation of Post-Prandial Lipid Metabolism in Obesity Linked Diabetes

Ian James Martins1,2,3*

¹School of Medical Sciences, Edith Cowan University, Australia

²School of Psychiatry and Clinical Neurosciences, University of Western Australia, Australia

³McCusker Alzheimer’s Research Foundation, Holywood Medical Centre, Australia

*Corresponding author: Ian James Martins, School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia

Received: September 23, 2016; Accepted: September 29, 2016; Published: October 03, 2016


Food; Restriction; Mitochondria; Metabolism; Post-prandial; Sirtuin 1; Insulin resistance


In various communities in the developing and developed world the understanding of the ingestion of a healthy diet [1] and hepatic fat metabolism has become of critical importance to the treatment of obesity linked Type 2 diabetes that is now linked to various organ diseases [2]. In the developing world transition to healthy diets has become urgent to prevent insulin resistance [3,4] and the obesity pandemic [5-8]. The liver is the major organ for the metabolism of dietary fat and after consumption of a meal in healthy individuals the fat is rapidly metabolized by the liver. In obesity linked Type 2 diabetes the post-prandial metabolism of a fat meal by the liver is defective with fat transport to the adipocyte relevant to adipocyte and brain appetite centre dysfunction [9-11] (Figure 1). In obese and diabetic mice post-prandial lipid metabolism has been shown to be defective with defects in the appetite centre associated with hyperglycemia and hyperphagia. Activation of hepatic fat metabolism with restricted food intake in these rodent studies may be relevant to adipocyte lipid metabolism and adipocyte signals that relate to appetite control [12] are vital to the treatment of obesity linked diabetes [13].

Interests in appetite control with food restriction of ingested fat in chronic diseases has accelerated to reduce plasma chylomicrons and lipoproteins that contain bacterial Lipopolysaccharides (LPS), lipophilic xenobiotics and lipophilic drugs that may be toxic to mitochondrial biogenesis with delayed post-prandial metabolism related to liver and adipose mitochondrial apoptosis. Interest in lipid science and technology has accelerated to reverse mitochondrial apoptosis [14] that is now a major defect in obesity linked diabetes and autonomous organ disease [11]. Appetite control involves nitric oxide consumption [15] and foods that contain excessive nitric oxide should be avoided and food restricted to maintain mitochondrial apoptosis versus mitochondrial biogenesis [16-18].

The treatment of obesity linked diabetes by appetite control now identifies the appetite gene Sirtuin 1 (Sirt 1) as the gene involved in nitric oxide metabolism, defective lipid metabolism in various tissues such as the adipocyte, liver and brain [19] with relevance to improved post-prandial lipid metabolism and relevant to reversal of obesity and Type 3 diabetes [20]. Sirt 1 regulation is critical for insulin therapy and mitochondrial biogenesis with appetite control essential to improve post-prandial metabolism. Nutritional regulation of Sirt 1 in many tissues is linked to mitochondrial biogenesis and inhibitors such as palmitic acid/LPS of nuclear receptor Sirt 1 is associated with appetite dysregulation by interference with neuropeptides (neuropeptide Y, brain derived neurotrophic factor) and endocrine hormones such as thyroid hormone that are linked to mitochondrial biogenesis [21,22].

Appetite control in rodents and man can be measured with relevance to Sirt 1 regulation of Fibroblast Growth Factor 21 (FGF21) that has effects on the central nervous system and injected FGF21 therapy has become important to the treatment of metabolic stress in obesity and diabetes [23-25]. In the aging process the delayed postprandial lipid metabolism is connected with inactivation of the AMPActivated Protein Kinase (AMPK)-Sirt 1 pathway that is responsible for mitochondrial biogenesis and nitric oxide homeostasis [26-28] with FGF21 essential for this integrated signaling network [29]. FGF21 therapy has important implications to the treatment of obesity linked diabetes with activation of the adipose tissue cross-talk associated with accelerated hepatic lipid metabolism.

Assessment of gene-environment interactions that regulate mitochondrial biogenesis have become of major research interest to the survival of the species with a single gene such as Sirt 1 defective and involved with nutrigenomic diet treatment in global populations [30]. In the developing world the obesity and diabetes epidemic may indicate that specific activators (magnesium, zinc) of Sirt 1 may be decreased in the plasma of these insulin resistant individuals. Magnesium is an important activator of Sirt 1 with connections to both appetite control and mitochondrial biogenesis [31]. Magnesium therapy is important to maintenance of glucose control and duration and amount of food intake may be relevant to magnesium binding to cell membranes to maintain magnesium/Sirt 1 cellular functions.

In the developing world the gene-environment interactions may have changed with relevance to the global aluminium industry. Aluminium has specific cell membrane lipid binding sites [15] with interactions with phosphatidylinositol and 1-palmitoyl-2-oleolylphosphatidylcholine and food levels of aluminium indicate that consumption of aluminium may have reached between 3-12 mg/ day [15]. The relevance to magnesium therapy indicate possible competition between aluminium and magnesium for lipid membrane binding sites [15] with increased magnesium consumption required to prevent membrane lipid peroxidation by aluminium [32]. Zinc deficiency in obesity has been reported in global populations with relevance to appetite and mitochondrial biogenesis but excessive zinc replacement should be monitored carefully with relevance to interference with magnesium absorption [33-36]. Foods that are contaminated with LPS should be restricted for consumption with relevance to LPS effects on zinc and magnesium deficiency [1,30,37,38].

In obesity linked diabetes the use of magnesium therapy in mi- RNA stability may be essential for Sirt 1 regulation of hepatic lipid metabolism to prevent liver steatosis and NAFLD [31]. Zinc deficiency is associated with increased expression of mi-RNA 34a in cells [39,40] with mi-RNA 34a involved as a transactivation inhibitor of p53 [41] linked to p53/Sirt 1 [30] expression. Regulation of magnesium and zinc levels has become important in global populations to reduce miR-34a levels and maintain mitochondrial biogenesis and prevent the development of liver steatosis and NAFLD [42]. In the developing world the rising plasma LPS levels associated with antibiotic resistance [43] induce a direct p53 associated mitochondrial dysfunction that interfere with hepatic lipid metabolism and induce NAFLD [30,37,44,45]. Mi-RNA 34a is released by many cells and tissues with elevated mi-RNA 34a associated with cardiac disease [46,47] and blood brain barrier disruption [48] with zinc deficiency and magnesium deficiency involved in brain appetite centre dysregulation.


The development of hyperphagia is associated with accelerated corruption of the adipose tissue-liver crosstalk with delayed postprandial lipid metabolism associated with mitochondrial apoptosis and liver disease. In the developing world the rising LPS levels delay post-prandial lipid metabolism in individuals with obesity-linked diabetes and food restriction is required to reduce nitric oxide consumption to maintain mitochondrial biogenesis. Healthy diets lower the defective transcriptional activation of nuclear receptors by miR-34a/Sirt 1 interactions and allow effective FGF21 therapy via AMPK-Sirt 1 signaling with relevance to nitric oxide and appetite control that involve neuropeptide and endocrine hormone interactions. In the developed world the nature of the food system (magnesium/zinc/aluminium) and its distribution [49] may be relevant to mitochondrial apoptosis with delayed post-prandial lipid metabolism involved in the induction of global obesity-linked diabetes. Consumption of appropriate magnesium and zinc levels are needed to regulate the appetite centre, prevent hyperphagia and activate the adipose tissue-liver interactions to accelerate the hepatic metabolism of fats.


This work was supported by grants from Edith Cowan University, the McCusker Alzheimer’s Research Foundation and the National Health and Medical Research Council.


  1. Martins IJ. Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases. Int J Mol Sci. 2015; 16: 29554-29573.
  2. Martins IJ. Diabetes and Organ Dysfunction in the Developing and Developed. World Global J Med Res. 2015; 15: 1-6.
  3. Nolan CJ, Ruderman NB, Kahn SE, Pedersen O, Prentki M. Insulin resistance as a physiological defense against metabolic stress: implications for the management of subsets of type 2 diabetes. Diabetes. 2015; 64: 673-686.
  4. Pansuria M, Xi H, Li L, Yang XF, Wang H. Insulin resistance, metabolic stress, and atherosclerosis. Front Biosci (Schol Ed). 2012; 4: 916-931.
  5. Popkin BM, Adair LS, Ng SW. Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev. 2012; 70: 3-21.
  6. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011; 378: 804-814.
  7. Frayn KN, Arner P, Yki-Järvinen H. Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem. 2006; 42: 89-103.
  8. Frayn KN. Insulin resistance, impaired postprandial lipid metabolism and abdominal obesity. A deadly triad. Med Princ Pract. 2002; 11: 31-40.
  9. Trayhurn P, Bing C. Appetite and energy balance signals from adipocytes. Philos Trans R Soc Lond B Biol Sci. 2006; 361: 1237-1249.
  10. Martins IJ. Lambert BOOK APPETITE ISBN 978-3-659-40372-901Appetite dysregulation and obesity in Western Countries. Ebook; 2015. First edited by Emma Jones. LAP LAMBERT Academic Publishing. ISBN: 978-3-659-40372-9. 2013.
  11. Martins IJ. Anti-Aging Genes Improve Appetite Regulation and Reverse Cell Senescence and Apoptosis in Global Populations. Advances in Aging Research. 2016; 5: 9-26.
  12. Coppari R, Ramadori G, Elmquist JK. The role of transcriptional regulators in central control of appetite and body weight. Nat Clin Pract Endocrinol Metab. 2009; 5: 160-166.
  13. Ahima RS, Antwi DA. Brain regulation of appetite and satiety. Endocrinol Metab Clin North Am. 2008; 37: 811-823.
  14. Heinonen S, Buzkova J, Muniandy M, Kaksonen R, Ollikainen M, Ismail K, et al. Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity. Diabetes. 2015; 64: 3135-3145.
  15. Martins IJ. Nutritional diets accelerate amyloid beta metabolism and prevent the induction of chronic diseases and Alzheimer’s disease. Photon ebooks. 2015; 1: 1-48.
  16. Nisoli E, Carruba MO. Nitric oxide and mitochondrial biogenesis.J Cell Sci. 2006; 119: 2855-2862.
  17. Boyd CS, Cadenas E. Nitric oxide and cell signaling pathways in mitochondrial-dependent apoptosis. Biol Chem. 2002; 383: 411-423.
  18. Brown GC, Borutaite V. Nitric oxide, mitochondria, and cell death. IUBMB Life. 2001; 52: 189-195.
  19. Gong H, Pang J, Han Y, Dai Y, Dai D, Cai J, et al. Age-dependent tissue expression patterns of Sirt1 in senescence-accelerated mice. Mol Med Rep. 2014; 10: 3296-3302.
  20. Martins IJ. Diet and Nutrition reverse Type 3 Diabetes and Accelerated Aging linked to Global chronic diseases. J Diab Res Ther. 2016; 2: 1-6.
  21. Goglia F, Silvestri E, Lanni A. Thyroid hormones and mitochondria. Biosci Rep. 2002; 22: 17-32.
  22. Harper ME, Seifert EL. Thyroid hormone effects on mitochondrial energetics. Thyroid. 2008; 18: 145-156.
  23. Cuevas-Ramos D, Aguilar-Salinas CA, Gómez-Pérez FJ. Metabolic actions of fibroblast growth factor 21. Curr Opin Pediatr. 2012; 24: 523-529.
  24. So WY, Leung PS. Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus. Med Res Rev. 2016; 36: 672-704.
  25. Foltz IN, Hu S, King C, Wu X, Yang C, Wang W, et al. Treating diabetes and obesity with an FGF21-mimetic antibody activating the βKlotho/FGFR1c receptor complex. Sci Transl Med. 2012; 4: 162ra153.
  26. Zhu S, Ma L, Wu Y, Ye X, Zhang T, Zhang Q, et al. FGF21 treatment ameliorates alcoholic fatty liver through activation of AMPK-SIRT1 pathway. Acta Biochim Biophys Sin (Shanghai). 2014; 46: 1041-1048.
  27. Chau MD, Gao J, Yang Q, Wu Z, Gromada J. Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci, USA. 2010; 107: 12553-12558.
  28. Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev. 2012; 11: 230-241.
  29. O'Neill HM, Holloway GP, Steinberg GR. AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity. Mol Cell Endocrinol. 2013; 366: 135-151.
  30. Martins IJ. Unhealthy Nutrigenomic Diets Accelerate NAFLD and Adiposity in Global communities. J Mol Genet Med. 2015; 9: 1-11.
  31. Martins IJ. Magnesium Therapy Prevents Senescence with the Reversal of Diabetes and Alzheimer ’s disease. Health. 2016; 8: 694-710.
  32. Dominguez MC, Sole E, Goñi C, Ballabriga A. Effect of aluminum and lead salts on lipid peroxidation and cell survival in human skin fibroblasts. Biol Trace Elem Res. 1995; 47: 57-67.
  33. Wessells KR, Brown KH. Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One. 2012; 7: e50568.
  34. de Leeuw IH, van Gaal L, Vanroelen W. Magnesium and obesity: effects of treatment on magnesium and other parameters. Magnesium. 1987; 6: 40-47.
  35. Farhanghi MA, Mahboob S, Ostadrahimi A. Obesity induced magnesium deficiency can be treated by vitamin D supplementation. J Pak Med Assoc. 2009; 59: 258-261.
  36. Spencer H, Norris C, Williams D. Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. J Am Coll Nutr. 1994; 13: 479-484.
  37. Martins IJ. Bacterial Lipopolysaccharides Change Membrane Fluidity with Relevance to Phospholipid and Amyloid Beta Dynamics in Alzheimer’s disease. J Microb Biochem Technol. 2016; 8: 322-324.
  38. Shea-Budgell M, Dojka M, Nimmo M, Lee D, Xu Z. Marginal zinc deficiency increased the susceptibility to acute lipopolysaccharide-induced liver injury in rats. Exp Biol Med (Maywood). 2006; 231: 553-558.
  39. Liuzzi J, Valencia K, Cao J, Gonzalez. A Zinc deficiency increases miR-34a expression in mice. Faseb J. 2011; 25: 1.
  40. Liuzzi JP. Up-Regulation of miR-34a by Zinc Deficiency. Vitam Miner. 2014; 3: 119.
  41. Navarro F, Lieberman J. miR-34 and p53: New Insights into a Complex Functional Relationship. PLoS One. 2015; 10: e0132767.
  42. Ding J, Li M, Wan X, Jin X, Chen S, Yu C, et al. Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease. Sci Rep. 2015; 5: 13729.
  43. Levy SB. Factors impacting on the problem of antibiotic resistance. J. Antimicrob. Chemother. 2002; 49: 25-30.
  44. Vaseva AV, Moll UM. The mitochondrial p53 pathway. Biochim Biophys Acta. 2009; 1787: 414-420.
  45. Saleem A, Adhihetty PJ, Hood DA. Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle. Physiol Genomics. 2009; 37: 58-66.
  46. Boon RA, Iekushi K, Lechner S, Seeger T, Fischer A, Heydt S, et al. MicroRNA-34a regulates cardiac ageing and function. Nature. 2013; 495: 107-410.
  47. Arunachalam G, Lakshmanan AP, Samuel SM, Triggle CR, Ding H. Molecular Interplay between microRNA-34a and Sirtuin1 in Hyperglycemia-Mediated Impaired Angiogenesis in Endothelial Cells: Effects of Metformin. J Pharmacol Exp Ther. 2016; 356: 314-323.
  48. Bukeirat M, Sarkar SN, Hu H, Quintana DD, Simpkins JW, Ren X. MiR-34a regulates blood-brain barrier permeability and mitochondrial function by targeting cytochrome c. J Cereb Blood Flow Metab. 2016; 36: 387-392.
  49. Wessells KR, Brown KH. Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One. 2012; 7: e50568.

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Citation: Martins IJ. Appetite Control with Relevance to Mitochondrial Biogenesis and Activation of Post-Prandial Lipid Metabolism in Obesity Linked Diabetes. Ann Obes Disord. 2016; 1(3): 1012.

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