Adaptive changes in zonation for gluconeogenic capacity in liver lobules of cold-exposed rats

Shiota, Masakazu; Fujimoto, Yasuyuki; Inagami, M.; Hiramatsu, Masayuki; Moriyama, Mitsuaki; Kimura, Kazuhiro; Ohta, Mitsuaki; Sugano, Tsukasa

doi:10.1152/ajpendo.1993.265.4.e559

Cited by 8 publications

(10 citation statements)

References 17 publications

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“…Moreover, this ratio is decreased by treatment with glucagon in vitro [4] and by diabetes in vivo (L. Agius, personal communication). In this respect it is noteworthy that the specific PV induction of hepatic long-chain fatty acid oxidation upon cold exposure reported in the present study agrees with the specific increase in gluconeogenesis in the PV zone of the liver under similar conditions reported by Shiota et al [39]. The physiological significance of these observations is unclear, since PV hepatocytes apparently constitute only a minor fraction of the parenchymal cells within the liver acinus [1,2].…”

Section: Discussionsupporting

confidence: 89%

Flexibility of zonation of fatty acid oxidation in rat liver

Guzmán

Bijleveld

Geelen

1995

Biochemical Journal

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Periportal and perivenous hepatocytes were isolated from rats subjected to different treatments that induce (starvation, cold exposure) or depress (refeeding after starvation) hepatic fatty acid oxidation. These experiments were designed to determine factors that may be involved in creating and maintaining the asymmetrical distribution of this metabolic pathway in the acinus of the liver. The uneven distribution of mitochondrial [14C]-palmitate oxidation within the acinus (i) was very flexible and changed markedly with the physiological status of the animal (periportal/perivenous ratio: 1.5, 2.0, 1.0 and 0.4 for fed, starved, refed and cold-exposed animals respectively), (ii) coincided with a similar zonation of carnitine palmitoyltransferase I activity in fed as well as in cold-exposed animals, (iii) was paralleled by a comparable zonation of mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase activity in starved animals, and (iv) was not determined by zonal differences in any of the following parameters: sensitivity of carnitine palmitoyltransferase I to malonyl-CoA, intracellular concentration of malonyl-CoA, fatty acid synthesizing capacity, acetyl-CoA carboxylase activity, fatty acid synthase activity or relative content of the two hepatic acetyl-CoA carboxylase isoforms. Unlike mitochondrial oxidation, peroxisomal [14C]palmitate oxidation was always zonated towards the perivenous zone of the liver irrespective of the physiological status of the animal. The data presented show that changes in the acinar distribution of mitochondrial long-chain fatty acid oxidation involve specific long-term mechanisms under different physiological conditions.

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Section: Discussionsupporting

confidence: 89%

Flexibility of zonation of fatty acid oxidation in rat liver

Guzmán

Bijleveld

Geelen

1995

Biochemical Journal

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“…Specifically, in situations where elevations in liver glucose production are warranted, e.g., chronic exposure to cold or acute exercise, the HGN capacity becomes selectively higher from the perivenous compared to the periportal zone, making the entire liver more homogenous as it pertains to its glucose production potential. 34,35 As such, any decrement in gluconeogenic potential from the perivenous zone could result in a lower capacity for glucose production from the entire liver. The culmination of these past reports 19,31,32 led us to suspect sex differences in glucose homeostasis following chronic alcohol consumption.…”

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 99%

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Sumida

Hill

Matveyenko³

2007

Clinical Medicine & Research

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Alcohol-induced hypoglycemia has traditionally been attributed to the amount of ethanol consumed rather than any inherent decline in glucose output capacity by the gluconeogenic organs and/or an increase in skeletal muscle glucose uptake. Further, while the potential for sex differences that might impact glucose homeostasis following chronic alcohol consumption has been recognized, direct evidence has been noticeably absent. This paper will provide a brief review of past and present reports of the potential for sex differences in glucose homeostasis following chronic ethanol consumption. This paper will also provide direct evidence from our laboratory demonstrating sex differences from chronic alcohol consumption resulting in a decrement in glucose appearance and more importantly, a specific decline in hepatic gluconeogenic (HGN) capacity in the absence and presence of ethanol. All our studies involved 8 weeks of chronic alcohol consumption in male and female Wistar rats, as well as a 24 to 48 hour fast to deplete hepatic glycogen stores. Under the conditions of chronic alcohol consumption and an acute dose of ethanol, we provide in vivo evidence of an early decline in whole body glucose appearance in females fed an ethanol diet compared to controls.While the decline was also observed in males fed the alcohol diet, it occurred much later compared to ethanol fed females. The site for the decline in whole body glucose production (i.e., either the kidneys or the liver) was beyond the scope of our prior in vivo study. In a follow-up study using the in situ perfused liver preparation, we provide additional evidence for a specific reduction in HGN capacity from lactate in ethanol fed females compared to ethanol fed males in the absence of alcohol in the perfusion medium. Finally, employing the isolated hepatocyte technique, we report decrements in HGN from lactate in ethanol fed females compared to ethanol fed males in the presence of ethanol in the incubation medium.The mechanism for the specific decline in HGN within the liver of ethanol fed females remains to be determined.To the extent that our observations in animals can be extrapolated to humans, we conclude that alcoholic women are more susceptible to ethanol-induced hypoglycemia compared to alcoholic men.

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“…The data can only be explained by differences in the relative contributions of glycerol versus lactate/ pyruvate to triose phosphate formation and glucose production, resulting in different labeling of triose phosphates between cell populations. If the labeling of triose phosphates were not uniform, differences in absolute rates of glucose production between cell populations would further decrease f. There is evidence that the activity of phosphoenolpyruvate carboxykinase (PEPCK) is zonated with periportal/perivenous activity ratios ranging from 1.5 to 3.0 (32)(33)(34)(35). Thus, because glycerol kinase activity is not zonated (Table II), cells of periportal origin with high PEPCK activity, when incubated with unlabeled glycerol ϩ […”

Section: Table I Rates Of Substrate Infusion and Of Glucose Productiomentioning

confidence: 99%

Limitations of the Mass Isotopomer Distribution Analysis of Glucose to Study Gluconeogenesis

Previs

Hallowell

Neimanis

et al. 1998

Journal of Biological Chemistry

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We ascribed the labeling heterogeneity to major decreases in glycerol concentration and enrichment across the liver. We concluded that [13 C]glycerol is unsuitable for tracing the contribution of gluconeogenesis to total glucose production. We now report isotopic heterogeneity of gluconeogenesis in hepatocytes, even when all cells are in contact with identical concentrations and enrichments of gluconeogenic substrates. Total rat hepatocytes were incubated with concentrations of glycerol, lactate, and pyruvate that were kept constant by substrate infusions. To modulate competition between substrates, the (glycerol)/(lactate ؉ pyruvate) infusion ratio ranged from 0.23 to 3.60. Metabolic and isotopic steady states were achieved in all cases. The apparent contribution of gluconeogenesis to glucose production (f) was calculated from the mass isotopomer distribution of glucose. When all substrates were 13 Clabeled, f was 97%, as expected in glycogen-deprived hepatocytes. As the infusion ratio ([ 13 C]glycerol)/(lactate ؉ pyruvate) increased, f increased from 73% to 94%. In contrast, as the infusion ratio (glycerol)/([ 13 C]lactate ؉ [ 13 C]pyruvate) increased, f decreased from 93% to 76%. In all cases, f increased with the rate of supply of the substrate that was labeled. Variations in f show that the 13 C labeling of triose phosphates was not equal in all hepatocytes, even when exposed to the same substrate concentrations and enrichments. We also showed that zonation of glycerol kinase activity is minor in rat liver. We conclude that zonation of other processes than glycerol phosphorylation contributes to the heterogeneity of triose phosphate labeling from glycerol in rat liver.

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Adaptive changes in zonation for gluconeogenic capacity in liver lobules of cold-exposed rats

Cited by 8 publications

References 17 publications

Flexibility of zonation of fatty acid oxidation in rat liver

Flexibility of zonation of fatty acid oxidation in rat liver

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Limitations of the Mass Isotopomer Distribution Analysis of Glucose to Study Gluconeogenesis

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