Obesity: considerations about etiology, metabolism, and the use of experimental models

Figures & data

Figure 1 Evidence suggests that the mechanisms inhibiting both appetite and caloric ingestion may be impaired in obese individuals.⁴⁸

Note: This is not yet consensual in the literature, although many authors have been trying to clarify how the mechanisms regulating hunger and satiety behave in this population. Reproduced with the permission of The American Physiological Society from Little TJ, Horowitz M, Feinle-Bisset C. Modulation by high-fat diets of gastrointestinal function and hormones associated with the regulation of energy intake: implications for the pathophysiology of obesity. Am J Clin Nutr. 2007;86(3):531–541.
Abbreviations: CCK, cholecystokinin; GLP-1, glucagon-like peptide 1; OXM, oxyntomodulin; PP, pancreatic polypeptide; PYY, peptide YY.

Figure 2 Postulated mechanisms for fatty acid control of gene transcription.¹⁰⁴ The FA per se, FA-CoA, or FA metabolite modulate (±) transcription of a responsive gene, encoding a protein involved in FA transport or metabolism, through various non-mutually selective potential mechanisms. Step 1: a signal transduction cascade is initiated to induce a covalent modification of a TF, thereby modifying its transcriptional potency. Step 2: the FA itself or its derivative acts as a ligand for a TF, which then can bind DNA at a FA response element and activate or repress transcription. Steps 3, 4 and 5: FA can act indirectly via alteration in either TF mRNA stability (Step 3) or gene transcription (Step 4), resulting in variations of de novo TF synthesis (Step 5) with an impact on the transcription rate of genes encoding proteins involved in FA transport or metabolism. On binding to the eognate response element, TF acts either as a monomer (Step 6), a homodimer, or a heterodimer with TF⁺, a different TF (Step 7).

Notes: Reproduced with the permission of the American Society for Biochemistry and Molecular Biology from Duplus E, Glorian M, Forest C. Fatty acid regulation of gene transcription. J Biol Chem. 2000;275(40):30749–30752. Copyright © 2000, by the American Society for Biochemistry and Molecular Biology.
Abbreviations: FA, fatty acids; FA-CoA, fatty acyl-CoA; TF, transcription factor.

Table 1 Amino acid processes in muscle metabolism and their respective enzymes, yielding tricarboxylic acid cycle intermediates

Amino acids	Enzymes	Intermediates
Aspartate	Aspartate aminotransferase	Oxaloacetate
Asparagine	Asparagine aminotransferase	Oxaloacetate
Isoleucine	Leucine aminotransferase	Acetyl-CoA and Propionil-CoA
Leucine	Leucine aminotransferase	Acetyl-CoA
Valine	Valine aminotransferase	Succinate

Abbreviation: CoA, coenzyme A.

Figure 3 Adaptation of muscle metabolism to a high availability of lipids.

Note: Reduced participation of carbohydrates and high amino acid participation in anaplerotic reactions are observed, activating the hexosamine pathway.
Abbreviations: AA, amino acid; CHO, carbohydrate; CoA, coenzyme A; NH₃, ammonia.

Figure 4 Micrograph of mitochondrial impairment caused by aspartate and asparagine supplementation in a rat model.

Notes: The left panel shows the soleus muscle of the sedentary control group (15,000×) and the right panel shows the soleus muscle of the supplemented group (aspartate and asparagine) (7000×).¹¹⁷

Little TJ Horowitz M Feinle-Bisset C Modulation by high-fat diets of gastrointestinal function and hormones associated with the regulation of energy intake: implications for the pathophysiology of obesity Am J Clin Nutr 2007 86 3 531 541 17823414

 PubMed Web of Science ®Google Scholar

Duplus E Glorian M Forest C Fatty acid regulation of gene transcription J Biol Chem 2000 275 40 30749 30752 10934217

 PubMed Web of Science ®Google Scholar

Lancha AHJr Effect of amino acids supplementation (aspartate and asparagine) upon glucose transport in rat skeletal muscle PhD thesis Sao Paulo University of Sao Paulo 1997 Portuguese

 Google Scholar