Certain white adipose tissue (WAT) depots are readily able to convert to a ''brown-like'' state with prolonged cold exposure or exposure to b-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1a protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia.

SUMMARY PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise, but has no effects on muscle strength or hypertrophy. We have identified a novel form of PGC-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength, and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a novel PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.

The Infrared Array Camera (IRAC) is one of three focal plane instruments in the Spitzer Space Telescope. IRAC is a four-channel camera that obtains simultaneous broad-band images at 3.6, 4.5, 5.8, and 8.0 µm. Two nearly adjacent 5.2×5.2 arcmin fields of view in the focal plane are viewed by the four channels in pairs (3.6 and 5.8 µm; 4.5 and 8 µm). All four detector arrays in the camera are 256×256 pixels in size, with the two shorter wavelength channels using InSb and the two longer wavelength channels using Si:As IBC detectors. IRAC is a powerful survey instrument because of its high sensitivity, large field of view, and four-color imaging. This paper summarizes the in-flight scientific, technical, and operational performance of IRAC.

Summary Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is elevated resting energy expenditure, which has been linked to increased brown fat thermogenesis1-6. How tumors induce brown fat activity is unknown. Here, using lewis lung carcinoma model of cancer cachexia, we show that tumor-derived PTHrP plays an important role in wasting by driving thermogenic gene expression in adipose tissues. Neutralization of PTHrP in tumor-bearing mice blocks adipose tissue browning and also loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for fighting cancer cachexia and improving patient survival.