title: Deficiency of glycerol-3-phosphate acyltransferase 1 decreases triacylglycerol storage and induces fatty acid oxidation in insect fat body.
abstract: Glycerol-3-phosphate acyltransferases (GPAT) catalyze the initial and rate-limiting step for the de novo synthesis of triacylglycerol (TAG). Four mammalian GPAT isoforms have been identified: the mitochondria-associated GPAT1 and 2, and the endoplasmic reticulum (ER)-associated GPAT3 and 4. In the insect Rhodnius prolixus, a vector of Chagas' disease, we previously predicted a mitochondrial-like isoform (RhoprGPAT1) from genomic data. In the current study, we clone the RhoprGPAT1 coding sequence and identify an ER-associated GPAT (RhoprGPAT4) as the second isoform in the insect. RhoprGPAT1 contributes 15% of the total GPAT activity in anterior midgut, 50% in posterior midgut and fat body, and 70% in the ovary. The RhoprGpat1 gene is the predominant transcript in the midgut and fat body. To evaluate the physiological relevance of RhoprGPAT1, we generate RhoprGPAT1-deficient insects. The knockdown of RhoprGpat1 results in 50% and 65% decrease in TAG content in the posterior midgut and fat body, respectively. RhoprGpat1-deficient insects also exhibits impaired lipid droplet expansion and a 2-fold increase in fatty acid β-oxidation rates in the fat body. We propose that the RhoprGPAT1 mitochondrial-like isoform is required to channel fatty acyl chains towards TAG synthesis and away from β-oxidation. Such a process is crucial for the insect lipid homeostasis.
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Alves-Bezerra
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Isabela B
authors.initials: IB
authors.lastname: Ramos
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Iron F
authors.initials: IF
authors.lastname: De Paula
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Maya-Monteiro
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Klett
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Coleman
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: katia@bioqmed.ufrj.br.
authors.forename: Katia C
authors.initials: KC
authors.lastname: Gondim
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005216:Fat Body / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D007313:Insecta / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D012239:Rhodnius / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D014280:Triglycerides; D005992:Glycerol-3-Phosphate O-Acyltransferase
keywords: Beta-oxidation; Fatty acid metabolism; Fatty acid oxidation; Insect physiology; Lipids; Triacylglycerol synthesis