title: Tissue-specific effects of leptin administration on the abundance of mitochondrial proteins during neonatal development.
abstract: Many tissues undergo a rapid transition after birth, accompanied by dramatic changes in mitochondrial protein function. In particular, uncoupling protein (UCP) abundance increases at birth in the lung and adipose tissue, to then gradually decline, an adaptation that is important in enabling normal tissue function. Leptin potentially mediates some of these changes and is known to promote the loss of UCP1 from brown fat but its effects on UCP2 and related mitochondrial proteins (i.e. voltage-dependent anion channel (VDAC) and cytochrome c) in other tissues are unknown. We therefore determined the effects of once-daily jugular venous administration of ovine recombinant leptin on mitochondrial protein abundance as determined by immunoblotting in tissues that do (i.e. the brain and pancreas) and do not (i.e. liver and skeletal muscle) express UCP2. Eight pairs of 1-day-old lambs received either 100 mug leptin or vehicle daily for 6 days, before tissue sampling on day 7. Administration of leptin diminished UCP2 abundance in the pancreas, but not the brain. Leptin administration had no affect on the abundance of VDAC or cytochrome c in any tissue examined. In leptin-administered animals, but not controls, UCP2 abundance in the pancreas was positively correlated with VDAC and cytochrome c content, and UCP2 abundance in the brain with colonic temperature. In conclusion, leptin administration to neonatal lambs causes a tissue-specific loss of UCP2 from the pancreas. These effects may be important in the regulation of neonatal tissue development and potentially for optimising metabolic control mechanisms in later life.
authors.affiliation: Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Gnanalingham
authors.forename: A
authors.initials: A
authors.lastname: Mostyn
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Webb
authors.forename: D H
authors.initials: DH
authors.lastname: Keisler
authors.forename: N
authors.initials: N
authors.lastname: Raver
authors.forename: M C
authors.initials: MC
authors.lastname: Alves-Guerra
authors.forename: C
authors.initials: C
authors.lastname: Pecqueur
authors.forename: B
authors.initials: B
authors.lastname: Miroux
authors.forename: T
authors.initials: T
authors.lastname: Stephenson
authors.forename: M E
authors.initials: ME
authors.lastname: Symonds
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000502:physiology; D045304:Cytochromes c / Q000032:analysis / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015151:Immunoblotting; D007262:Infusions, Intravenous; D007473:Ion Channels; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D018709:Statistics, Nonparametric; D000071246:Uncoupling Protein 2; D050994:Voltage-Dependent Anion Channels / Q000032:analysis / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011994:Recombinant Proteins; D000071246:Uncoupling Protein 2; D050994:Voltage-Dependent Anion Channels; D045304:Cytochromes c