Alcohol, Vol. 9, pp. 93-94, 1992
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Effect of Ethanol Administration on Plasma Glycerol Levels in the Rat E D W A R D A. C A R T E R
Department o f Pediatrics, Harvard Medical School and the Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, M A 02114 Received 28 M a y 1991; Accepted 12 September 1991 CARTER, E. A. Effect of ethanol administration on plasma glycerol levels in the rat. ALCOHOL 9(2) 93-94, 1992.Many mechanisms have been postulated as being responsible for the fatty liver resulting from ethanol ingestion. Lipid mobilization has been strongly implicated in both acute and chronic ethanol administration-the difference between the two lying in the source of the fat. In the acute situation, the lipid is mobilized from depot fat, whereas in the chronic situation, it apparently comes from the diet. One possibility not explored is the mobilization of glycerol. This substance is the backbone of triglyceride. Hence, an influx of glycerol to the liver coupled with increased amounts of fatty acids could help explain, in part, the fatty liver resulting from alcohol administration. The purpose of the following study was to determine if such an effect does occur. Fatty liver
Ethanol
Plasma glycerol
FEMALE Sprague-Dawley rats (weighing 200 g) were used throughout these studies. Some animals were fed a normal test diet, or normal diet modified to contain either 1%0 orotic acid (w/w), 68% glucose (percent calories), 64% protein (percent calories), no fat or no protein. Other animals were fed the "super diet" (6) or the high-alcohol liquid diet (7) for 28 days. Another group received a single dose of ethanol (7.5 g/ kg) or glucose (13.7 g/kg), 18 h before sacrifice. All animals were exsanguinated via aorta under ether anesthesia. Plasma glycerol content of the deproteinized samples were determined as described previously (2) using a Ferrand fluorometer equipped with interference filters 465 MU for emission and 351 MU for excitation.
Having thus established that the method used could detect changes in plasma glycerol content, we were anxious to see what effect acute or chronic ethanol administration would produce. As shown in Table 2, ethanol given acutely or chronically by two different dietary methods had no effect on plasma glycerol levels. As shown previously in this and other laboratories, the single dose of ethanol caused a four-fold increase in hepatic triglyceride content (11), as did the high ethanol liquid diet (7). With the super diet, the hepatic triglyceride content was actually lower than the control, as had been reported earlier (6). The plasma content of the alcohol-treated rats did not differ from that of the control receiving amounts of glucose or sucrose isocaloric to the ethanol. The liquid diet (alcohol and control) did result in plasma glycerol levels higher than those of the untreated rats. The reason(s) for this were not explored in this study.
RESULTS The effect of various dietary measures on the plasma glycerol content is illustrated in Table 1. A 7-day feeding of diet containing 1%0 orotic acid resulted in a marked increase in glycerol content. Fourteen days on a protein-free diet led to a marked decrease whereas animals fed a high glucose or fatfree diet for the same length of time exhibited increased plasma glycerol levels. Two weeks on the high-protein free diet had no effect on the plasma glycerol content.
DISCUSSION Glycerol is predominantly metabolized by the liver (10) in mammalian organisms and is rapidly converted to glucose and lipids or oxidized to CO2. Recently, it was suggested that ethanol in vitro had a stimulatory effect on glycerol release from rat adipose tissue (1). However, the amount of ethanol re-
Requests for reprints should be addressed to Edward A. Carter, PhD, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA 02114. 93
94
CARTER TABLE 1 EFFECT OF VARIOUSDIETARY CONDITIONSON PLASMA GLYCEROL LEVELS Diet
No. of Animals
Control (untreated) Orotic acid Protein-free High protein High glucose Fat-free
7 5 4 4 5 9
Plasma Glycerol (g/ml plasma mean _+ SD)
Days on Diet -
6.89 16.30 4.50 8.08 9.85 12.11
7 14 14 14 14
± 0.73 + 2.86 ± 1.0 + 2.89 _+ 2.12 ± 1.61
p-Value -
0741-8329/92$5.00 + .00 Copyright©1992PergamonPress Ltd.
Printedin the U.S.A. All rightsreserved.
Effect of Ethanol Administration on Plasma Glycerol Levels in the Rat E D W A R D A. C A R T E R
Department o f Pediatrics, Harvard Medical School and the Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, M A 02114 Received 28 M a y 1991; Accepted 12 September 1991 CARTER, E. A. Effect of ethanol administration on plasma glycerol levels in the rat. ALCOHOL 9(2) 93-94, 1992.Many mechanisms have been postulated as being responsible for the fatty liver resulting from ethanol ingestion. Lipid mobilization has been strongly implicated in both acute and chronic ethanol administration-the difference between the two lying in the source of the fat. In the acute situation, the lipid is mobilized from depot fat, whereas in the chronic situation, it apparently comes from the diet. One possibility not explored is the mobilization of glycerol. This substance is the backbone of triglyceride. Hence, an influx of glycerol to the liver coupled with increased amounts of fatty acids could help explain, in part, the fatty liver resulting from alcohol administration. The purpose of the following study was to determine if such an effect does occur. Fatty liver
Ethanol
Plasma glycerol
FEMALE Sprague-Dawley rats (weighing 200 g) were used throughout these studies. Some animals were fed a normal test diet, or normal diet modified to contain either 1%0 orotic acid (w/w), 68% glucose (percent calories), 64% protein (percent calories), no fat or no protein. Other animals were fed the "super diet" (6) or the high-alcohol liquid diet (7) for 28 days. Another group received a single dose of ethanol (7.5 g/ kg) or glucose (13.7 g/kg), 18 h before sacrifice. All animals were exsanguinated via aorta under ether anesthesia. Plasma glycerol content of the deproteinized samples were determined as described previously (2) using a Ferrand fluorometer equipped with interference filters 465 MU for emission and 351 MU for excitation.
Having thus established that the method used could detect changes in plasma glycerol content, we were anxious to see what effect acute or chronic ethanol administration would produce. As shown in Table 2, ethanol given acutely or chronically by two different dietary methods had no effect on plasma glycerol levels. As shown previously in this and other laboratories, the single dose of ethanol caused a four-fold increase in hepatic triglyceride content (11), as did the high ethanol liquid diet (7). With the super diet, the hepatic triglyceride content was actually lower than the control, as had been reported earlier (6). The plasma content of the alcohol-treated rats did not differ from that of the control receiving amounts of glucose or sucrose isocaloric to the ethanol. The liquid diet (alcohol and control) did result in plasma glycerol levels higher than those of the untreated rats. The reason(s) for this were not explored in this study.
RESULTS The effect of various dietary measures on the plasma glycerol content is illustrated in Table 1. A 7-day feeding of diet containing 1%0 orotic acid resulted in a marked increase in glycerol content. Fourteen days on a protein-free diet led to a marked decrease whereas animals fed a high glucose or fatfree diet for the same length of time exhibited increased plasma glycerol levels. Two weeks on the high-protein free diet had no effect on the plasma glycerol content.
DISCUSSION Glycerol is predominantly metabolized by the liver (10) in mammalian organisms and is rapidly converted to glucose and lipids or oxidized to CO2. Recently, it was suggested that ethanol in vitro had a stimulatory effect on glycerol release from rat adipose tissue (1). However, the amount of ethanol re-
Requests for reprints should be addressed to Edward A. Carter, PhD, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA 02114. 93
94
CARTER TABLE 1 EFFECT OF VARIOUSDIETARY CONDITIONSON PLASMA GLYCEROL LEVELS Diet
No. of Animals
Control (untreated) Orotic acid Protein-free High protein High glucose Fat-free
7 5 4 4 5 9
Plasma Glycerol (g/ml plasma mean _+ SD)
Days on Diet -
6.89 16.30 4.50 8.08 9.85 12.11
7 14 14 14 14
± 0.73 + 2.86 ± 1.0 + 2.89 _+ 2.12 ± 1.61
p-Value -
