Local blockade of tacrolimus promotes T-cell-mediated tumor regression in systemically immunosuppressed hosts.

Background: Immunosuppressive drugs such as tacrolimus have revolutionized our ability to transplant organs between individuals. Tacrolimus acts systemically to suppress the activity of T-cells within and around transplanted organs. However, tacrolimus also suppresses T-cell function in the skin, contributing to a high incidence of skin cancer and associated mortality and morbidity in solid organ transplant recipients.

Ppargamma2 is a key driver of longevity in the mouse.

Aging involves a progressive physiological remodeling that is controlled by both genetic and environmental factors. Many of these factors impact also on white adipose tissue (WAT), which has been shown to be a determinant of lifespan. Interrogating a transcriptional network for predicted causal regulatory interactions in a collection of mouse WAT from F2 crosses with a seed set of 60 known longevity genes, we identified a novel transcriptional subnetwork of 742 genes which represent thus-far-unknown longevity genes.

Promoter-, cell-, and ligand-specific transactivation responses of the VDRB1 isoform.

The vitamin D receptor (VDR) mediates the effects of 1,25(OH)(2)D(3), the active form of vitamin D. The human VDRB1 isoform differs from the originally described VDR by an N-terminal extension of 50 amino acids. Here we investigate cell-, promoter-, and ligand-specific transactivation by the VDRB1 isoform.

Enhanced bone formation in lipodystrophic PPARgamma(hyp/hyp) mice relocates haematopoiesis to the spleen.

The peroxisome proliferator-activated receptor gamma (PPARgamma) controls adipogenesis and metabolism. We demonstrate here that the absence of PPARgamma in fat has potent osteogenic activities, which affect haematopoiesis. The congenital absence of PPARgamma in fat of lipodystrophic PPARgamma(hyp/hyp) mice, strongly enhanced bone mass and consequentially reduced the bone-marrow cavity.

Peroxisome proliferator-activated receptor-gamma: too much of a good thing causes harm.

The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) helps to translate 'what you eat' into 'what you are' because it allows dietary fatty acids (PPARgamma ligands) to modulate gene transcription. Treatments for diabetes include PPARgamma activators, as they sensitize the body to insulin. Our understanding of PPARgamma function has recently been enhanced by a flurry of human and mouse genetic studies, and the characterization of new PPARgamma ligands.

Leptin: cutting the fat off the bone.

Context: Leptin was initially proposed to be the antiobesity hormone. Now it is realised that leptin is more a signal molecule that communicates nutritional status to the brain, and that it is involved in bone formation by having an antiosteogenic action.

Starting Point: Recently, Florent Elefteriou and colleagues (Endocrinology 2003; 144: 3842-47) found that hypothalamic neurons control bone mass.

Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPAR gamma 2-specific exon B, resulting in a white adipose tissue knockdown of PPAR gamma. Although homozygous (PPAR gamma hyp/hyp) mice are born with similar weight as the WT mice, the PPAR gamma hyp/hyp animals become growth retarded and develop severe lipodystrophy and hyperlipidemia.