Adrenergic receptor signaling in adipocytes controls not only the hydrolysis of triglycerides as fuel for other organs but is also a driver of brown adipocyte thermogenesis and energy consumption. As the appearance of these mitochondria-rich, thermogenically active cells in 'white' adipocyte depots is correlated with resistance to overnutrition and glucose intolerance, the molecular basis of their genesis and metabolic activity needs to be understood. b-adrenergic receptors regulate the enzymatic machinery for lipolysis and fuel utilization. They also coordinately stimulate the transcription of genes that support the specific functions of white and brown adipocytes. They accomplish this through the activation of a network of signaling pathways that include cAMP-dependent protein kinase and members of the mitogen-activated protein kinase family. In brown adipocytes, these kinases control the transcription of nuclear factors such as peroxisome proliferator-activated receptor-g coactivator-1s, as well as other molecules discovered to respond to adrenergic signals, to increase mitochondrial biogenesis and uncoupling protein-1 (UCP1) expression. However, it is also important to understand the mechanisms that may actively repress these energy-wasting processes. Toward that end, we provide evidence for an important role for the nuclear receptor LXRa as a cAMP-and oxysterol-dependent transcriptional repressor of the Ucp1 gene. Adipocytes from LXRa-null mice have increased expression of most 'markers' of brown adipocytes, increased mitochondrial mass and uncoupled respiration. These studies reveal potential new targets and directions for controlling the relative levels of white versus brown adipocytes as a means of metabolic fuel utilization in the struggle against obesity and related metabolic diseases.

Expansion of (AGC)n repeats has been associated with genetic disorders called triplet-repeat diseases such as Huntington's disease (HD), myotonic muscular dystrophy (DM) and Kennedy's disease. To gain insight into the abnormal behavior of these repeats, we studied their structural properties in supercoiled DNA. Chemical probing revealed that, under physiological salt and pH conditions, Zn2+ or Co2+ ions induce (AGC)n repeats to adopt a novel non-B DNA structure in which all cytosine but none of adenine residues in either strand become unpaired. The minimum size of (AGC)n repeat that could form this structure independently of neighboring sequences is a single unit of double-stranded trinucleotide, 5'AGC3'/5'GCT3'. Other trinucleotide units of the same nucleotide composition, 5'CAG3'/5'CTG3' or 5'GCA3'/5'TGC3', do not form non-B DNA structures. This unusual DNA structural properly adopted by a single 5'AGC3'/5'GCT3' trinucleotide may contribute to expansion of (AGC)n sequences in triplet-repeat diseases.