Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans.

Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients.

Renal cell carcinoma following bariatric surgery.

BACKGROUND: Obesity, hypertension, smoking, and amphetamine diet pills increase the risk for renal cell carcinoma (RCC). Obesity causes a four-fold increase. We report our 11-year experience with RCC after bariatric operations. METHODS: 5 patients with RCC were identified out of 2,287 bariatric surgical patients since 1993 on retrospective chart review. RESULTS: 4 of the 5 patients were females. At time of their bariatric operation, patients were age 29-52 (43.4) years, weighed 109-158 (129.8) kg, and BMI was 43-60 (49.4). All tumors were incidentally discovered 8-66 (27.4) months postoperatively when the patients weighed 54-94 (71.4) kg, with BMI 21-34 (26.6). Preoperative renal ultrasound obtained within 3 months of the bariatric operation was normal in 4; the other did not have a preoperative study. The latter patient had a vertical banded gastroplasty 12 years before and the RCC was discovered 5 1/2 years later during work-up for a revision. 3 had a distal gastric bypass and 1 underwent adjustable gastric banding. 4 of the patients had a radical nephrectomy and 1 underwent a partial nephrectomy. Tumors were 2.0-8.7 (4.4) cm in size, and all were clear-cell RCC without vascular or extrarenal involvement. None has had recurrence at 3-67 (30.8) months follow-up. 1 patient died from a stroke 18 months later. CONCLUSION: Reversal of obesity following bariatric surgery does not eliminate risk for RCC. Preoperative and annual postoperative ultrasonography may be useful in identifying early stage RCC. Lesions that are not pure cysts must be evaluated with CT scans or MRI. Nephrectomy may be curative.

Tea catechin synergies in inhibition of cancer cell proliferation and of a cancer specific cell surface oxidase (ECTO-NOX).

The anticancer properties of tea catechins are most frequently attributed to the principal catechin (-)-epigallocatechin-3-gallate (EGCg). Efficacy was evaluated using growth of cultured HeLa cells and inhibition of the enzymatic activity of a putative cell surface tea target enzyme, a cancer-associated cell surface-located NADH oxidase (ECTO-NOX) designated tNOX. The amounts of EGCg required to inhibit by both criteria was reduced 10 times by combination with inactive catechins such as (-)-epicatechin (EC), (-)-epigallocatechin (EGC) or (-)-epicatechin-3-gallate (ECG). Various synthetic mixtures based on purified catechins and decaffeinated tea extracts treated enzymatically to reduce the ester bond-containing catechins varying in EGCg content from 0.065 to 40% were of comparable efficacy to decaffeinated green tea extracts as long as EGCg was present and the ratio of total catechins to EGCg + EGC was about 1.5. Such mixtures appear to offer potential cancer protection and therapeutic advantages over those of EGCg alone through lowered toxicity of the mixture to normal cells and for more efficient blood delivery of orally-administered catechins to a tumour site.