Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting.

The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-alpha as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (alpha1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.

Increased leptin expression in mice with bacterial peritonitis is partially regulated by tumor necrosis factor alpha.

Plasma leptin and ob gene mRNA levels were increased in mice following bacterial peritonitis, and blocking an endogenous tumor necrosis factor alpha (TNF-alpha) response blunted the increase. However, plasma leptin concentrations did not correlate with the associated anorexia. We conclude that leptin expression is under partial regulatory control of TNF-alpha in peritonitis, but the anorexia is not dependent on increased leptin production.

Breast arterial calcification: association with coronary artery disease. Work in progress.

PURPOSE: To assess the association between mammographically detected breast arterial calcification (BAC) and coronary artery disease (CAD) and diabetes mellitus (DM). MATERIALS AND METHODS: The records of 182 women (aged 39-92 years) who underwent both mammography and coronary arteriography were retrospectively reviewed to determine BAC, CAD, and DM status. RESULTS: For women aged less than 59 years (under-59 group) (n = 54), nearly all women with BAC (n = 8) had CAD (n = 7) and also had DM (n = 6). For this group, the positive predictive value of BAC for CAD was 0.88 and the negative predictive value was 0.65 (chi 2 = 7.7, P < .05). DM was a confounding variable. The positive predictive value of DM for CAD increased from 0.62 when BAC was absent to 1.00 when BAC was present (standard error of difference, .22; P < .10). No significant association between BAC and CAD was found for women aged 59 years and older (n = 128). CONCLUSION: BAC in women aged less than 59 years may indicate an additional risk factor for CAD, particularly in diabetic patients.