Glycerol turnover and oxidation in man

Bortz, Walter M.; Paul, Prabir Kumar; Haff, Agnes C.; Holmes, William L.

doi:10.1172/jci106950

Cited by 212 publications

(110 citation statements)

References 21 publications

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“…By contrast, although glycerol concentrations late in lactation are high (0.52 mmol/l), concentrations observed early in lactation are comparable to those observed in obese humans fasted for 3 wk (0.25 vs. 0.29 mmol/l; Ref. 7). Glycerol concentrations observed after the molt are intermediate between those observed early and late in lactation, but the mean glycerol R a is nearly three times lower and similar to that observed in fasting humans, suggesting an increased need for NEFA availability during lactation.…”

Section: Discussionsupporting

confidence: 52%

“…Values measured early and late in lactation (8.0 and 7.4 mol⅐kg Ϫ1 ⅐min Ϫ1 , respectively) are substantially higher than values observed in humans that are either postabsorptive (ϳ3.1 mol⅐kg Ϫ1 ⅐min Ϫ1 ) or fasted from 3-4 days to 3 wk (4.2-5.3 mol⅐kg Ϫ1 ⅐min Ϫ1 ; Refs. 2,7,12). By contrast, although glycerol concentrations late in lactation are high (0.52 mmol/l), concentrations observed early in lactation are comparable to those observed in obese humans fasted for 3 wk (0.25 vs. 0.29 mmol/l; Ref.…”

Section: Discussionmentioning

confidence: 61%

“…In the postabsorptive state, the conversion of glycerol to glucose accounts for ϳ3-4.5% of glucose production; however, after fasting for several days, the contribution of glycerol to glucose production increases to ϳ10 -22% (2,7,29). After weeks of fasting glycerol can contribute up to 60% of glucose production (7), although the basis for this calculation has come into question because of methodological issues related to the separation of radiolabeled glycerol from radiolabeled glucose (2). Thus, during long-duration fasts, the availability of lipid stores not only serves to provide energy via fatty acid oxidation but also contributes to meeting the energetic costs of glucose-dependent tissues.…”

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confidence: 99%

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Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Houser¹,

Champagne²,

Crocker³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Adult female elephant seals (Mirounga angustirostris) combine long-term fasting with lactation and molting. Glycerol gluconeogenesis has been hypothesized as potentially meeting all of the glucose requirements of the seals during these fasts. To test this hypothesis, a primed constant infusion of [2-14 C]glycerol was administered to 10 ten adult female elephant seals at 5 and 21-22 days postpartum and to 10 additional adult females immediately after the molt. Glycerol kinetics, rates of lipolysis, and the contribution of glycerol to glucose production were determined for each period. Plasma metabolite levels as well as insulin, glucagon, and cortisol were also measured. Glycerol rate of appearance was not significantly correlated with mass (P ϭ 0.14, r 2 ϭ 0.33) but was significantly related to the percentage of glucose derived from glycerol (P Ͻ 0.01, r 2 ϭ 0.81) during late lactation. The contribution of glycerol to glucose production was Ͻ3% during each fasting period, suggesting a lower contribution to gluconeogenesis than is observed in other long-term fasting mammals. Because of a high rate of endogenous glucose production in fasting elephant seals, it is likely that glycerol gluconeogenesis still makes a substantial contribution to the substrate needs of glucose-dependent tissues. The lack of a relationship between glucoregulatory hormones and glycerol kinetics, glycerol gluconeogenesis, and metabolites supports the proposition that fasting elephant seals do not conform to the traditional insulinglucagon model of substrate metabolism. reesterification; lipid metabolism; lactogenesis; glucagon; insulin GLUCONEOGENESIS IS an important physiological process in maintaining blood glucose levels during fasting and can meet Ͼ90% of glucose needs after just 2 days of fasting (28). Both amino acids and glycerol can be metabolized to glucose when exogenous carbohydrate becomes unavailable. However, under long-term fasting conditions the loss of protein is generally minimized to stay the eventual loss of organ function that results from protein depletion. Under these conditions glycerol becomes an increasingly important gluconeogenic precursor. In the postabsorptive state, the conversion of glycerol to glucose accounts for ϳ3-4.5% of glucose production; however, after fasting for several days, the contribution of glycerol to glucose production increases to ϳ10 -22% (2, 7, 29). After weeks of fasting glycerol can contribute up to 60% of glucose production (7), although the basis for this calculation has come into question because of methodological issues related to the separation of radiolabeled glycerol from radiolabeled glucose (2). Thus, during long-duration fasts, the availability of lipid stores not only serves to provide energy via fatty acid oxidation but also contributes to meeting the energetic costs of glucose-dependent tissues.Northern elephant seals (Mirounga angustirostris) undertake prolonged fasts of 1-3 mo. Adult females undertake two fasts each year, one while lactating and another while molting. Bot...

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 61%

mentioning

confidence: 99%

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Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Houser¹,

Champagne²,

Crocker³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The rate of glucose production directly measured by Owen et al (1998) by splanchnic and renal catherization (479 mmolamin 124 gad) agrees well with rate of glucose turnover, measured isotopically, in starving obese man (Bortz, 1972) and is a good estimate of the rate of gluconeogenesis required in this situation. The major gluconeogenic substrates were lactate, glycerol and amino acids, with glutamine being the major renal substrate.…”

Section: Prandial Gluconeogenesissupporting

confidence: 71%

Comments on metabolic needs for glucose and the role of gluconeogenesis

1999

Eur J Clin Nutr

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The metabolism of carbohydrates is largely determined by their chemical properties. Glucose may have been selected, over the other aldohexoses, because of its low propensity for glycation of proteins. That carbohydrate is stored in polymeric form (glycogen) is dictated by osmotic pressure considerations. That stored fat is about eight times more calorically dense than glycogen, when attendant water is factored in, accounts for the predominance of fat as a storage form of calories and, also, for the fact that ingested carbohydrate is oxidized promptly (that is, fuel of the fed state) rather than being extensively stored. That stored glycogen is accompanied by so much water accounts for the fact that the brain only has very small glycogen stores. Carbohydrate has two important advantages, over fat, as a metabolic fuel; it is the only fuel that can produce ATP in the absence of oxygen, and more ATP is produced per O 2 consumed when glucose is oxidized, compared with when fat is oxidized. These advantages probably determine the preference of many cell types for carbohydrate. In addition to its use as a metabolic fuel, glucose plays other important roles such as provision of NADPH via the pentose phosphate pathway, and as a source material for the synthesis of other key carbohydrates, for example, ribose and deoxyribose for nucleic acid synthesis and substrates for the synthesis of glycoproteins, glycolipids and glycosaminoglycans. It can also play a key role in anaplerosis. Although it is widely acknowledged that gluconeogenesis plays a crucial role in starvation it is now apparent that prandial gluconeogenesis occurs, both in the metabolic disposal of dietary amino acids and in the synthesis of glycogen by the indirect pathway. Although there is, strictly speaking, no dietary requirement for carbohydrate it is evident that glucose is a universal fuel for probably all cells in the body and carbohydrate is the cheapest source of calories and the major source of dietary ®bre. These observations, together with the fact that glucose is the preferred metabolic fuel for the brain, permit us to recommend appreciable quantities of carbohydrate in all prudent diets. Why carbohydrate?Since fat has a much higher caloric density than carbohydrate it is worth considering, at the outset, why we have a carbohydrate metabolism. Without question, this is due to the fact that carbohydrate is the primary product of photosynthesis and, since heterotrophic animals obtain their energy from autotrophic organisms, it was inevitable that they evolved a metabolism that extracted useful energy from the most abundantly available carbon source Ð carbohydrate. Why did glucose, of all the sugars, become the primary carbohydrate for energy metabolism? Precise answers to such a question are not readily available but it must be pointed out that glucose has the lowest proportion of straight-chain (non-ring) structure of all the aldohexoses. This minimizes non-enzymatic protein glycation and, indeed, Bunn & Higgins (1981) have suggested that evolution...

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“…The Ra of glycerol in healthy subjects fasted long term is estimated to be about 5 µmol/kg body weight per min and this value is about twice that after an overnight fast (Bortz et al 1972;Hetenyi et al 1983;Klein et al 1986). …”

Section: Whole-body Glycerol Productionmentioning

confidence: 97%

Glycerol production and utilization measured using stable isotopes

Landau

1999

Proc. Nutr. Soc.

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The rate of appearance of glycerol in the systemic circulation is determined from the enrichment of arterial blood glycerol when labelled glycerol is infused intravenously. This value provides a good measure of whole-body lipolysis during fasting, except that arterial infusion and venous sampling, if feasible, would probably give a higher more-accurate value. Lipolysis occurs primarily in adipose tissue, although other tissues contribute, notably muscle. Measurement is based on the difference in the enrichment of the glycerol entering and leaving the tissue. Lipolysis is underestimated by the extent to which glycerol released by lipolysis does not enter the systemic circulation, as occurs when lipolysis takes place in the non-hepatic tissue of the splanchnic bed. Glycerol released into the systemic circulation is utilized mainly by liver, although kidney and muscle are also major users of glycerol. Measurement of glycerol utilization is based on the amount of labelled glycerol taken up by the tissues. Other tissues probably utilize glycerol to a smaller extent, but in total this represents a significant amount. Most glycerol taken up by liver is converted to glucose. Glucose is probably the major source of glycerol-3-phosphate used in the esterification of fatty acids by adipose tissue.

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Glycerol turnover and oxidation in man

Cited by 212 publications

References 21 publications

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Comments on metabolic needs for glucose and the role of gluconeogenesis

Glycerol production and utilization measured using stable isotopes

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