Xing Xian Yu

Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation

Mitochondrial uncoupling proteins have been implicated in the maintenance of metabolic rate and adaptational thermoregulation. We recently reported the identification of a brain‐specific mitochondrial uncoupling protein homologue, UCP4. Here we characterized another newly described member of the uncoupling protein family, termed UCP5 (also called BMCP1). UCP5 transcripts are present in multiple human and mouse tissues, with an especially high abundance in the brain and testis. Expression of UCP5 in mammalian cells reduces the mitochondrial membrane potential. Multiple isoforms of UCP5 were identified and exhibited tissue‐specific distribution and different potency in reduction of membrane potential. Furthermore, the mRNA abundance of both UCP4 and UCP5 is modulated by nutritional status or temperature in a tissue‐specific manner in mice. Brain UCP4 and UCP5 mRNA transcripts rose by 1.5‐ and 1.7‐fold, respectively, and liver UCP5 expression increased by 1.8‐fold in response to acute cold exposure. A high‐fat diet increased UCP5 mRNA in liver by 1.6‐fold selectively in the obesity‐resistant A/J but not in the obesity‐prone C57BL/6J mouse strain. Liver UCP5 expression decreased significantly with a 24 h fast and was restored to the normal level after refeeding. In contrast, brain transcripts for both genes were not significantly altered by fasting or high‐fat diet. These findings are consistent with the notion that UCP4 and UCP5 may be involved in tissue‐specific thermoregulation and metabolic changes associated with nutritional status.–Yu, X. X., Mao, W., Zhong, A., Schow, P., Brush, J., Sherwood, S. W., Adams, S. H., Pan, G. Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation. FASEB J. 14, 1611–1618 (2000)

Cold elicits the simultaneous induction of fatty acid synthesis and β-oxidation in murine brown adipose tissue: prediction from differential gene expression and confirmation in vivo

A survey of genes differentially expressed in the brown adipose tissue (BAT) of mice exposed to a range of environmental temperatures was carried out to identify novel genes and pathways associated with the transition of this tissue toward an amplified thermogenic state. The current report focuses on an analysis of the expression patterns of 50 metabolic genes in BAT under control conditions (22°C), cold exposure (4°C, 1 to 48 h), warm acclimation (33°C, 3 wk), or food restriction/meal feeding (animals fed the same amount as warm mice). In general, expression of genes encoding proteins involving glucose uptake and catabolism was significantly elevated in the BAT of cold‐exposed mice. The levels of mRNAs encoding proteins critical to de novo lipo‐genesis were also increased. Gene expression for enzymes associated with procurement and combustion of long chain fatty acids (LCFAs) was increased in the cold. Thus, a model was proposed in which coordinated activation of glucose uptake, fatty acid synthesis, and fatty acid combustion occurs as part of the adaptive thermogenic processes in BAT. Confirmation emerged from in vivo assessments of cold‐induced changes in BAT 2‐deoxyglucose uptake (increased 2.7‐fold), BAT lipogenesis (2.8‐fold higher), and incorporation of LCFA carboxyl‐carbon into BAT water‐soluble metabolites (elevated ~twofold). It is proposed that temperature‐sensitive regulation of distinct intracellular malo‐nyl‐CoA pool sizes plays an important role in driving this unique metabolic profile via maintenance of the lipogenic pool but diminution of the carnitine palmi‐toyltransferase 1 inhibitory pool under cold conditions.—Yu X. X., Lewin, D. A., Forrest, W. F., Adams S. H. Cold elicits the simultaneous induction of fatty acid synthesis and β‐oxidation in murine brown adipose tissue: prediction from differential gene expression and confirmation in vivo. FASEB J. 16, 155–168 (2002)

Response of Hepatic Mitochondrial and Peroxisomal β-Oxidation to Increasing Palmitate Concentrations in Piglets

Responses of total, mitochondrial, and peroxisomal beta-oxidation to increasing [1-14C]-palmitate concentrations (0.02-1.0 mM) were measured in liver homogenates from neonatal pigs. Incubations were conducted in the absence (total beta-oxidation) or presence (peroxisomal beta-oxidation) of antimycin A and rotenone; mitochondrial beta-oxidation was calculated as total minus peroxisomal oxidation. Total and mitochondrial beta-oxidations were maximized at a palmitate concentration of 0.05 mM, whereas peroxisomal beta-oxidation was maximized at 0.50 mM palmitate. Across concentrations, peroxisomal beta-oxidation contributed 40-47% of total beta-oxidation. An increased rate of CO2 production and a greater ratio of CO2 production to total mitochondrial beta-oxidation as palmitate concentration increased suggested that the limited capacity for mitochondrial beta-oxidation was attributable primarily to limited ketogenic capacity. Comparative observations in liver from adult rats showed that peroxisomal beta-oxidation was maximized at 0.1 mM palmitate, but total and mitochondrial beta-oxidation rates were not maximized even at 1 mM palmitate. At 1 mM palmitate, peroxisomal beta-oxidation was 20% of total beta-oxidation in adult rats and 37% in adult pigs. Therefore, the contribution of peroxisomal beta-oxidation to total beta-oxidation is highly dependent on substrate concentration and appears to be greater in adult pigs than in adult rats. The greater proportional contribution of peroxisomal beta-oxidation in piglet liver might act as a compensatory mechanism for piglets to oxidize milk fatty acids.