Resistance to visceral obesity is associated with increased locomotion in mice expressing an endothelial cell-specific fibroblast growth factor 1 transgene.

Overdevelopment of visceral adipose is positively correlated with the etiology of obesity-associated pathologies including cardiovascular disease and insulin resistance. However, identification of genetic, molecular, and physiological factors regulating adipose development and function in response to nutritional stress is incomplete. Fibroblast Growth Factor 1 (FGF1) is a cytokine expressed and released by both adipocytes and endothelial cells under hypoxia, thermal, and oxidative stress. Expression of Fibroblast Growth Factor 1 (FGF1) in adipose is required for normal depot development and remodeling. Loss of FGF1 leads to deleterious changes in adipose morphology, metabolism, and insulin resistance. Conversely, diabetic and obese mice injected with recombinant FGF1 display improvements in insulin sensitivity and a reduction in adiposity. We report in this novel, in vivo study that transgenic mice expressing an endothelial-specific FGF1 transgene (FGF1-Tek) are resistant to high-fat diet-induced abdominal adipose accretion and are more glucose-tolerant than wild-type control animals. Metabolic chamber analyses indicate that suppression of the development of visceral adiposity and insulin resistance was not associated with alterations in appetite or resting metabolic rate in the FGF1-Tek strain. Instead, FGF1-Tek mice display increased locomotor activity that likely promotes the utilization of dietary fatty acids before they can accumulate in adipose and liver. This study provides insight into the impact that genetic differences dictating the production of FGF1 has on the risk for developing obesity-related metabolic disease in response to nutritional stress.

Motor deficits, impaired response inhibition, and blunted response to methylphenidate following neonatal exposure to decabromodiphenyl ether.

Decabromodiphenyl ether (decaBDE) is an applied brominated flame retardant that is widely-used in electronic equipment. After decades of use, decaBDE and other members of its polybrominated diphenyl ether class have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Although it has been banned in Europe and voluntarily withdrawn from the U.S. market, it is still used in Asian countries. Evidence from epidemiological and animal studies indicate that decaBDE exposure targets brain development and produces behavioral impairments. The current study examined an array of motor and learning behaviors in a C57BL6/J mouse model to determine the breadth of the developmental neurotoxicity produced by decaBDE. Mouse pups were given a single daily oral dose of 0 or 20mg/kg decaBDE from postnatal day 1 to 21 and were tested in adulthood. Exposed male mice had impaired forelimb grip strength, altered motor output in a circadian wheel-running procedure, increased response errors during an operant differential reinforcement of low rates (DRL) procedure and a blunted response to an acute methylphenidate challenge administered before DRL testing. With the exception of altered wheel-running output, exposed females were not affected. Neither sex had altered somatic growth, motor coordination impairments on the Rotarod, gross learning deficits during operant lever-press acquisition, or impaired food motivation. The overall pattern of effects suggests that males are more sensitive to developmental decaBDE exposure, especially when performing behaviors that require effortful motor output or when learning tasks that require sufficient response inhibition for their successful completion.

The myoglobin gene of the Antarctic icefish, Chaenocephalus aceratus, contains a duplicated TATAAAA sequence that interferes with transcription.

Six of the 16 known species of Antarctic icefish (family Channichthyidae) have lost the ability to express cardiac myoglobin (Mb) via at least four independent events during radiation of these species. We report here that the lesion in Chaenocephalus aceratus Mb is a duplicated TATAAAA element that blocks transcription. This lesion is distinct from those of other icefish species that do not express cardiac Mb. The C. aceratus Mb gene is nearly identical to that of Chionodraco rastrospinosus, a closely related Mb-expressing icefish species, with one exception. A 15-bp segment is present in C. aceratus but absent from C. rastrospinosus; this insertion is located 648 bp upstream from the reference transcription start site of C. rastrospinosus and includes the sequence TATAAAA, which bound HeLa cell transcription factor IID (TFIID) and icefish nuclear proteins in gel-retardation assays. Reporter constructs containing the 'full-length' C. aceratus Mb promoter were not expressed in transient expression assays in oxidative skeletal muscle of live icefish. By contrast, constructs employing the nearly identical 'full-length' C. rastrospinosus Mb promoter were efficiently expressed in parallel assays in the same tissue. Truncated constructs of C. aceratus Mb that did not contain the 15-bp duplication were expressed at very low levels. These data confirm a third independent mechanism of Mb loss among channichthyid species, indicate that C. aceratus aerobic muscle is capable of expressing functional Mb genes and demonstrate that duplication of the muscle-specific TATAAAA sequence in an inappropriate context can result in loss of a gene's expression, resulting in significant physiological consequences.