Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability

Abstract

White adipose tissue (WAT) produces lactate in significant amount from circulating glucose, especially in obesity;Under normoxia, 3T3L1 cells secrete large quantities of lactate to the medium, again at the expense of glucose and proportionally to its levels. Most of the glucose was converted to lactate with only part of it being used to synthesize fat. Cultured adipocytes were largely anaerobic, but this was not a Warburg-like process. It is speculated that the massive production of lactate, is a process of defense of the adipocyte, used to dispose of excess glucose. This way, the adipocyte exports glucose carbon (and reduces the problem of excess substrate availability) to the liver, but the process may be also a mechanism of short-term control of hyperglycemia. The in vivo data obtained from adipose tissue of male rats agree with this interpretation.

A method for the measurement of lactate, glycerol and fatty acid production from14C-glucose in primary cultures of rat epididymal adipocytes

“…0.2 mM of dissolved O2). These values were in the range of those measured under the same conditions 28 . The calculated pCO2 was in the range of 5 kPa, corresponding to 1.7 mM of dissolved CO2 41 .…”

“…We have found, recently, that adipocytes glycolyze huge amounts of glucose to lactate and glycerol 28 , acting, essentially, as an anaerobic tissue under normoxic conditions, such as those used in the present study, and this mechanism extends to the in vivo conditions 29 . We have also found that WAT contains a full urea cycle 58 and a potentially active amino acid metabolism 14 .…”

“…via glycerol-3P) was considerable, even when corrected by the number of carbons. We can only assume that a significant part of the glycerol-3P pathway resulted in the patent presence of high specific activity-glycerol in the medium 28 . The results observed in the test of the method are, thus, coincident with those observed using other systems and conditions.…”

“…WAT consumed very little oxygen in vivo 78 , suggesting that its anaerobic glycolysis may sustain a sizeable amount of its needs 28 for an unexpectedly active metabolism 14 . In fact, about 98.5 % of the adult large adipocytes such as those used here is made up of fat, the small active cytosol, however, has enzyme activities (i.e.…”

“…Many studies on adipocytes have been done using standard murine cell lines, as we recently did, finding that, under normoxic conditions, 3T3L1 cells converted to lactate enormous amounts of the medium glucose 28 covering most of their energy needs through anaerobic glycolysis. We postulated that this "wasting" of glucose might actually help to diminish hyperglycemia because of the large combined mass of WAT; in ex vivo studies; we also observed the accumulation of lactate in WAT masses 29 , in line with the results previously observed in cultured cells.…”