Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

Macrophages infiltrate adipose tissue in obesity and are involved in the induction of inflammation, thereby contributing to the development of obesity-associated metabolic disorders. Here, we show that the macrophage-derived soluble protein AIM is endocytosed into adipocytes via CD36. Within adipocytes, AIM associates with cytosolic fatty acid synthase (FAS), thereby decreasing FAS activity. This decreases lipid droplet size, stimulating the efflux of free fatty acids and glycerol from adipocytes. As an additional consequence of FAS inhibition, AIM prevents preadipocyte maturation. In vivo, the increase in adipocyte size and fat weight induced by high-fat diet (HFD) was accelerated in AIM-deficient (AIM(-)(/-)) mice compared to AIM(+/+) mice. Moreover, injection of recombinant AIM in AIM(-)(/-) mice suppresses the increase in fat mass induced by HFD. Interestingly, metabolic rates are comparable in AIM(-)(/-) and AIM(+/+) mice, suggesting that AIM specifically influences adipocyte status. Thus, this AIM function in adipocytes may be physiologically relevant to obesity progression.

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The telomerase activity and length of telomeres of peripheral blood mononuclear cells obtained from 124 healthy individuals aged 4-95 years was measured. Telomerase activity level was semiquantitatively assessed by a fluorescent-telomeric repeat amplification protocol (fluorescent-TRAP) using an internal telomerase assay standard, fluorescent primers and an automated laser fluorescent DNA sequencer. Telomeric length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. TRF length was determined in 80 individuals and age-related progressive reduction of size was observed. TRF length in peripheral blood mononuclear cells obtained from normal individuals (aged 4-39 years) decreased by approximately 84 bp per year, while in individuals aged > or = 40 years it decreased by 41 bp per year. In contrast, telomerase activity showed an apparent biphasic pattern with aging. Individuals aged 4-39 years showed a progressive decrease in telomerase activity, whereas 65% of those aged > or = 40 years showed relatively stable but very low telomerase activity, and the remaining individuals aged > or = 40 years had no detectable telomerase activity. These data obtained from normal individuals might in the future be of value to help risk stratify and manage the care of patients with leukemia.

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