Abstract
Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins. Changes in the cellular BMP content therefore reflect an altered metabolic activity of the endolysosomal system. Surprisingly, little is known about the physiological regulation of BMP. In this study, we investigated the effects of nutritional and metabolic factors on BMP profiles of whole tissues and parenchymal and nonparenchymal cells. Tissue samples were obtained from fed, fasted, 2 h refed, and insulin-treated mice, as well as from mice housed at 5°C, 22°C, or 30°C. These tissues exhibited distinct BMP profiles that were regulated by the nutritional state in a tissue-specific manner. Insulin treatment was not sufficient to mimic refeeding-induced changes in tissue BMP levels, indicating that BMP metabolism is regulated by other hormonal or nutritional factors. Tissue fractionation experiments revealed that fasting drastically elevates BMP levels in hepatocytes and pancreatic cells. Furthermore, we observed that the BMP content in brown adipose tissue strongly depends on housing temperatures. In conclusion, our observations suggest that BMP concentrations adapt to the metabolic state in a tissue- and cell-type-specific manner in mice. Drastic changes observed in hepatocytes, pancreatic cells, and brown adipocytes suggest that BMP plays a role in the functional adaption to nutrient starvation and ambient temperature.
Highlights
Bis(monoacylglycero)phosphate (BMP), known as lysobisphosphatidic acid, is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins
Bis(monoacylglycero)phosphate (BMP), known as lysobisphosphatidic acid, is a phospholipid highly enriched in the intraluminal vesicles (ILVs) of late endosomes/lysosomes [1] and plays a key role in lysosomal cargo sorting
Refeeding decreased total BMP levels in brown adipose tissue (BAT), inguinal white adipose tissue (WAT), the kidney, the pancreas, and skeletal muscle, whereas increased levels were observed in the brain and small intestine (Fig. 1A)
Summary
Bis(monoacylglycero)phosphate (BMP), known as lysobisphosphatidic acid, is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins. Bis(monoacylglycero)phosphate (BMP), known as lysobisphosphatidic acid, is a phospholipid highly enriched in the intraluminal vesicles (ILVs) of late endosomes/lysosomes [1] and plays a key role in lysosomal cargo sorting. BMP is a structural isomer of phosphatidylglycerol that harbors one FA at each of the two glycerol moieties It has a unique sn-1-glycerophospho-sn-1′-glycerol stereoconformation, making it highly resistant to degradation by phospholipases of acidic organelles [2]. Changes in the cellular BMP content reflect ILV formation and degradation in acidic organelles and indicate an altered metabolic activity of endolysosomal
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