Obese and anorexic yeasts: Experimental models to understand the metabolic syndrome and lipotoxicity

• Published in: Biochimica et biophysica acta Vol. 1801; no. 3; pp. 222 - 229
• Main Author: Kohlwein, Sepp D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2010
• Subjects: AMP-activated protein kinase; Animals; Anorexia - metabolism; Apoptosis; Fatty acid toxicity; Fatty Acids - metabolism; Humans; Lipase - metabolism; Lipid Peroxidation; Lipidomics; Lipolysis; Metabolic Syndrome - metabolism; Models, Biological; Obesity - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe; TOR signaling; Unfolded protein response; AMP-activated protein kinase; Unfolded protein response; UPR; Schizosaccharomyces pombe; SCAP; Fatty acid toxicity; SREBP; ACSL; TOR signaling; DGAT; SCD-1; PKC; Lipidomics; PP2A; DAG; ER; Lipolysis; ERAD; PA; TOR; CDK1; AMPK; TAG; FA; Saccharomyces cerevisiae; Apoptosis
• ISSN: 1388-1981; 0006-3002; 1879-2618; 1878-2434
• DOI: 10.1016/j.bbalip.2009.12.016

Lipotoxicity is the pathological consequence of lipid overflow in non-adipose tissue, mediated through reactive lipid moieties which may even lead to lipid-induced cell death (lipoapoptosis). This derailment of cellular and organismal fat homeostasis is the consequence of obesity due to continued over-feeding, and contributes substantially to the pathogenesis of insulin resistance, type 2 diabetes mellitus and cardiovascular disease, which are all components of the metabolic syndrome. Now, does yeast, a single-celled eukaryote, ever suffer from the metabolic syndrome and what can we potentially learn from studies in this organism about the underlying molecular mechanism that lead to lipid-associated pathologies in human cells? In this review I will summarize the remarkably conserved metabolic and regulatory processes relevant to establishing cellular energy and lipid homeostasis, as well as recent findings that provide detailed insights into the molecular mechanisms underlying fat-induced cellular malfunction and cell death, with potential implications also for mammalian cells.