This report identifies a novel gene encoding 15-oxoprostaglandin-⌬ 13 -reductase (PGR-2), which catalyzes the reaction converting 15-keto-PGE 2 to 13,14-dihydro-15-keto-PGE 2 . The expression of PGR-2 is up-regulated in the late phase of 3T3-L1 adipocyte differentiation and predominantly distributed in adipose tissue. Overexpression of PGR-2 in cells decreases peroxisome proliferator-activated receptor ␥ (PPAR␥)-dependent transcription and prohibits 3T3-L1 adipocyte differentiation without affecting expression of PPAR␥. Interestingly, we found that 15-keto-PGE 2 can act as a ligand of PPAR␥ to increase coactivator recruitment, thus activating PPAR␥-mediated transcription and enhancing adipogenesis of 3T3-L1 cells. Overexpression of 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation reaction of PGE 2 to form 15-keto-PGE 2, significantly increased PPAR␥-mediated transcription in a PGE 2 -dependent manner. Reciprocally, overexpression of wild-type PGR-2, but not the catalytically defective mutant, abolished the effect of 15-keto-PGE 2 on PPAR␥ activation. These results demonstrate a novel link between catabolism of PGE 2 and regulation of ligand-induced PPAR␥ activation.
A new class of non-holonomic constraints is proposed, namely, completely nonholonomic, partially non-holonomic, and truly non-holonomic. The classification is mainly based on the Frobenius condition and the existence of the integral surfaces of the constraints. The intrinsic properties of non-holonomic constraints, such as the reachability property, vary with respect to different classes. In fact, some nonholonomic constraints do not have the reachability property. The path-planning problems for different classes of non-holonomic constraints also become quite delicate. The paths from a point on one side of the critical surface to a point on the other side must pass through the singular points on the critical surface. The observation made in this paper gives a new outlook of non-holonomic constraints, and may lead to a deeper understanding of the behaviour of systems with non-holonomic constraints.
Adipose tissue renewal and obesity-driven expansion of fat cell number are dependent on proliferation and differentiation of adipose progenitors that reside in the vasculature that develops in coordination with adipose depots. The transcriptional events that regulate commitment of progenitors to the adipose lineage are poorly understood. Because expression of the nuclear receptor PPARγ defines the adipose lineage, isolation of elements that control PPARγ expression in adipose precursors may lead to discovery of transcriptional regulators of early adipocyte determination. Here, we describe the identification and validation in transgenic mice of 5 highly conserved non-coding sequences from the PPARγ locus that can drive expression of a reporter gene in a manner that recapitulates the tissue-specific pattern of PPARγ expression. Surprisingly, these 5 elements appear to control PPARγ expression in adipocyte precursors that are associated with the vasculature of adipose depots, but not in mature adipocytes. Characterization of these five PPARγ regulatory sequences may enable isolation of the transcription factors that bind these cis elements and provide insight into the molecular regulation of adipose tissue expansion in normal and pathological states.
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