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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lactate metabolism is altered in obesity. Increasing obesity is associated with increased blood lactate levels after an overnight fast. In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity. In the present study, we systematically analyzed the relationship between insulin sensitivity (the Sensitivity Index [SI] derived using the minimal model), body mass index (BMI), and glucose, insulin, and lactate levels in the basal state and following intravenous (IV) glucose and insulin administration in lean and obese subjects. The results showed that SI and BMI were inversely related, as expected. Insulin sensitivity was more tightly associated with glucose, insulin, and lactate levels (both basal and integrated) than obesity per se. A significant inverse relationship was found between SI and basal lactate levels (r = -.56). Moreover, a significant and positive relationship was found between SI and incremental lactate area under the curve (reflecting acute lactate production) (r = .41). In a multiple regression analysis to separate the independent effects of obesity (BMI) and insulin sensitivity, after adjusting for age, sex, and race, SI accounted for 34% of the variance in basal lactate and 24% of the variance in incremental lactate area. Obesity independently accounted for 10% of the variance in basal lactate and 11% of the variance in incremental lactate area, neither of which were statistically significant. We conclude that elevations in basal lactate are associated with the development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin. 153 40

Estimates of the quantitative contribution of adipose tissue to whole-body glucose metabolism, previously reported as 1-3%, have been revised to be on the order of 10-30%. These revised estimates come, in part, from a recognition that adipose tissue uses glucose to produce lactate and pyruvate, in addition to CO2 and triglycerides. Lactate production by adipose tissue is modulated in vitro by changes in glucose, insulin, and epinephrine concentrations. In vivo, lactate production is regulated acutely by the animal's nutritional state (fed or fasted) and chronically by the degree of obesity. A strong positive correlation exists between rat fat cell size and relative conversion of glucose to lactate (r = 0.89, P less than 0.001). Diabetes is also associated with markedly increased lactate production in adipocytes. Fat cells from obese or diabetic rats (or humans) can metabolize to lactate as much as 50-70% of the glucose taken up. From these recent studies, a picture is emerging in which the adipose organ may provide lactate for hepatic gluconeogenesis during fasting, and also lactate for hepatic glycogen synthesis after food ingestion. Modulation of adipocyte lactate production and contribution of adipose tissue lactate to the body's fuel economy in physiological and pathological states are the focus of this review.
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PMID:Lactate production in adipose tissue: a regulated function with extra-adipose implications. 156 93

Generally obese and lean pigs in both the fed and fasted states were anesthetized and then acutely infused with increasing concentrations of the beta-adrenergic agonist isoproterenol. Plasma free fatty acid (FFA), blood glycerol, glucose and lactate, and heart rate were monitored during the infusion period. Data were reduced by estimating the parameters of the generalized logistic function (minimum, maximum, ED50 and slope) and subsequently analyzed to compare the lean and obese genotypes within nutritional state. Lactate data could not be fitted to this function because the upper asymptote was not approached during the experiment. The minimum plasma concentration of FFA tended (P less than .1) to be less in obese than in lean pigs. The maximum, ED50 and slope for the responses of FFA were similar for obese and lean pigs in fed pigs and in fasted pigs. In fed pigs, the minimum glycerol concentration was greater in obese than in lean pigs, and the ED50 for heart rate tended to be lower in lean than in obese pigs. All other estimated parameters for the variables were similar in fed obese and lean pigs. In fasted pigs, the maximum glucose concentration was greater in obese than in lean pigs. All other parameters for the variables were similar in fasted obese and lean pigs. The results suggest that there was no major defect in lipid mobilization in these obese pigs (only a lower minimum FFA concentration was detected) and that an increased maximum blood glucose concentration in the fasting state might contribute to the obesity.
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PMID:Lipid mobilization by obese and lean pigs infused with the beta-adrenergic agonist isoproterenol. 279 21

Release of lactate was studied during in vitro incubations with isolated fat cells. Lactate release increased (approximately 3-fold) with increasing medium glucose concentration (from 3 to 12 mM) in both large and small fat cells. Large fat cells from older, fatter rats, however, released 3-4 times more lactate per cell than small fat cells from young rats when incubated with 3, 6 or 12 mM glucose. Insulin and epinephrine produced a marked stimulation of lactate release in small fat cells, but these hormones had no effect in large fat cells. Lactate accounted for only 10-15% of the glucose metabolized by small fat cells under all incubation conditions but was nearly 40% of glucose utilized by large fat cells at glucose concentrations greater than 6 mM. In conclusion, lactate is a major metabolite of glucose in adipocytes, particularly in the large fat cells. Adipose tissue may therefore be a major site of lactate production, particularly in states of altered glucose metabolism (i.e., hyperglycemia) and obesity.
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PMID:Lactate release from isolated rat adipocytes: influence of cell size, glucose concentration, insulin and epinephrine. 635 Jan 39

Lactate and glycerol turnover is enhanced in obesity and NIDDM. To evaluate the influence of NIDDM on subcutaneous adipose tissue metabolism microdialysis combined with 133Xe clearance and measurements in arterialized plasma were carried out using samples of subcutaneous abdominal fat from nine obese NIDDM subjects (glucose, 7.9 +/- 0.7 mmol L-1) (mean +/- SEM) and nine obese non-diabetic subjects (glucose, 4.9 +/- 0.1) matched for age, BMI and body fat. After an overnight fast arterialized plasma levels were 1145 +/- 110 vs. 876 +/- 59 mumol L-1 (P < 0.05) for lactate and 75 +/- 10 vs. 66 +/- 8 mumol L-1 for glycerol in the diabetic and control group, respectively. The corresponding abdominal subcutaneous interstitial lactate and glycerol concentrations were 1278 +/- 63 vs 1107 +/- 64 mumol L-1 and 314 +/- 28 vs. 311 +/- 17 mumol L-1, respectively. However, adipose tissue blood flow in the same region was lower in NIDDM subjects (1.5 +/- 0.2 vs 2.4 +/- 0.3 mL 100 g-1 min-1) (P < 0.05). Consequently, apparent subcutaneous lactate and glycerol release, estimated according to Fick, were not statistically different in the two groups (1.8 +/- 0.4 vs 2.4 +/- 0.8 and 2.1 +/- 0.4 vs 3.1 +/- 0.5 mumol kg-1 min-1 in NIDDM and control subjects, respectively). Thus, in the post-absorptive state apparent lactate and glycerol release by the abdominal subcutaneous tissue in obese NIDDM subjects was similar to that in a matched group of obese non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microdialysis assessment of adipose tissue metabolism in post-absorptive obese NIDDM subjects. 758 14

We have examined the effect of peripheral 3-hydroxybutyrate injections on food intake and the contribution of the vagus nerve in the resistance to dietary fat-induced obesity in a rodent model. S 5B/Pl rats, which are resistant to dietary-fat induced obesity, and Osborne-Mendel rats, which are sensitive, were adapted to reverse light cycle. Food intake was measured for 24 h following the injection of 3-hydroxybutyrate, lactate, or glycerol (all 5 mMol/kg0.75, SC) at the onset of dark. Three-hydroxybutyrate reduced food intake (p < 0.0001) in S 5B/Pl rats only. Lactate reduced food intake slightly (p < 0.009) in both strains and glycerol had no effect on food intake. In a second experiment, S 5B/Pl and Osborne-Mendel rats were adapted to a high-fat diet and were then subjected to either selective hepatic vagotomy or sham operation. Vagotomy had no effect on weight gain of Osborne-Mendel rats but allowed weight gain in S 5B/Pl rats (p < 0.0001). Even in vagotomized S 5B/Pl rats, however, blood 3-hydroxybutyrate levels were inversely associated (r = -0.50) with food intake. These data suggest that the hepatic vagus nerve may contribute to the resistance of S 5B/Pl rats to dietary-fat induced obesity, but the data do not rule out a strictly central role for the regulation of food intake by 3-hydroxybutyrate in this strain.
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PMID:Peripheral 3-hydroxybutyrate and food intake in a model of dietary-fat induced obesity: effect of vagotomy. 766 4

Skeletal muscle contributes significantly to reduced insulin-stimulated glucose disposal in patients with obesity and non-insulin-dependent (type II) diabetes mellitus (NIDDM). The biochemical basis for insulin resistance is not known but may involve reduced glucose transport and/or a defect in intracellular pathways for glucose disposal. To address this question, we measured basal and insulin-stimulated glucose oxidation, glycogen formation, and nonoxidative glycolysis (lactate and amino acid release) in an incubated muscle preparation from nonobese and morbidly obese patients with and without NIDDM. Pathways of glucose disposal were also determined in muscle of obese NIDDM patients incubated under hyperglycemic (20 mmol/L) conditions, which increases glucose uptake by mass action. Under basal conditions (no insulin present) there were no significant differences in glycogen formation or glucose oxidation between nonobese control, obese nondiabetic, or obese diabetics. Lactate release was significantly higher in obese controls compared to nonobese controls in the basal state at 5 mmol/L glucose (10.2 +/- 2.8 v 24.7 +/- 3.5 nmol/min/g, P < .05). Under maximal insulin-stimulated conditions, rates of glycogen formation, glucose oxidation, and nonoxidized glycolysis increased 1.9-, 2.3-, and 2.2-fold over basal (P < .05) in nonobese controls. By contrast, insulin was ineffective at stimulating significant increases in any metabolic pathway of glucose disposal in muscle of obese or obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose metabolism in incubated human muscle: effect of obesity and non-insulin-dependent diabetes mellitus. 805 46

Adrenalectomy (ADX) lowers circulating glucose levels in animal models of non-insulin dependent diabetes (NIDDM) and obesity. To investigate the role of hepatic glucose production (HGP) and tissue glucose oxidation in the improvement in glucose tolerance, hepatocyte gluconeogenesis and the activity of pyruvate dehydrogenase (PDH) were examined in different tissues of gold thioglucose (GTG) obese mice 2 weeks after ADX or sham ADX. GTG-obese mice which had undergone ADX weighed significantly less than their adrenal intact counterparts (GTG ADX: 37.5 +/- 0.7 g; GTG: 44.1 +/- 0.4; p < 0.05), and demonstrated lower serum glucose (GTG ADX: 22.5 +/- 1.6 mmol/L; GTG: 29.4 +/- 1.9 mmol/L; p < 0.05) and serum insulin levels (GTG ADX: 76 +/- 10 microU/mL; GTG: 470 +/- 63 microU/mL; p < 0.05). Lactate conversion to glucose by hepatocytes isolated from ADX GTG mice was significantly reduced compared with that of hepatocytes from GTG mice (GTG ADX: 125 +/- 10 nmol glucose/10(6) cells; GTG: 403 +/- 65 nmol glucose/10(6) cells; p < 0.05). ADX also significantly reduced both the glycogen (GTG ADX: 165 +/- 27 mumol/liver; GTG: 614 +/- 60 mumol/liver; p < 0.05) and fatty acid content (GTG ADX: 101 +/- 9 mg fatty acid/g liver; GTG: 404 +/- 40 mg fatty acid/g liver; p < 0.05) of the liver of GTG-obese mice. ADX of GTG-obese mice reduced PDH activity by varying degrees in all tissues, except quadriceps muscle. These observations are consistent with an ADX induced decrease in hepatic lipid stores removing fatty acid-induced increases in gluconeogenesis and increased peripheral availability of fatty acids inhibiting PDH activity via the glucose/fatty acid cycle. It is also evident that the improvement in glucose tolerance which accompanies ADX of GTG-obese mice is not due to increased PDH activity resulting in enhanced peripheral glucose oxidation. Instead, it is more likely that reduced blood glucose levels after ADX of GTG-obese mice are the result of decreased gluconeogenesis in the liver.
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PMID:Hepatic gluconeogenesis and the activity of PDH in individual tissues of GTG-obese mice following adrenalectomy. 882 61

Abnormalities observed in intermediary metabolism may be related to the pathogenesis of obesity-related diseases such as type 2 diabetes. Glycerol and lactate production was estimated in the sc adipose tissue of two anatomical regions of 10 lean (LW), 10 obese (OW), and 10 matched diabetic (DW) black urban women. This was done with the sc microdialysis technique and combined with adipose tissue blood flow (ATBF) rates calculated from (133)Xe clearance. Biochemical measurements were made in the postabsorptive and postprandial state. Bioimpedance and computed tomography scans were used to define body composition. DW present with more visceral fat (DW, 138 +/- 5.0; OW, 66.6 +/- 5.0 cm; P < 0.01). This was associated with elevated free testosterone levels (DW, 1.21 +/- 0.1; OW, 0.75 +/- 0.1 nmol/L; P < 0.05). The fasting FFA, glycerol, and lactate levels increased across the three groups (LW < OW < DW). During the oral glucose tolerance test, glucose levels were elevated in DW, with higher insulin levels [0 h: DW, 207 +/- 8.6; OW, 100 +/- 7.2 pmol/L (P < 0.01); 1 h: DW, 410 +/- 15.2; OW, 320 +/- 10.9 pmol/L (P < 0.05)], but with a flat Cpeptide response (1 h: DW, 932 +/- 40; OW, 1764 +/- 40 pmol/L; P < 0.05). Plasma lactate levels increased significantly in LW and OW at 1 h (P < 0.001), but remained lower in LW vs. OW for all time points. ATBF was highest in LW [abdominal, 0 h: DW, 4.5 +/- 0.2; OW, 1.7 mL/100 g.min (P < 0.01); femoral, 0 h: DW, 3.4 +/- 0.2; OW, 1.8 +/- 0.3 mL/100 g.min (P < 0.01)]. ATBF did not increase in DW during the oral glucose tolerance test. Glycerol release (GR) was used to assess the lipolytic rate and was highest in LW in the abdominal area [0 h: LW, 1.7 +/- 0.2; OW, 1.1 +/- 0.2 micromol/kg.min (P < 0.05); DW, 0.78 +/- 0.05 micromol/kg.min (P < 0.05 vs. OW)]. By contrast, GR was higher in the femoral area of OW (0 h: OW, 1.6 +/- 0.2; LW, 1.15 +/- 0.1 micromol/kg.min; P < 0.05). Regional differences were observed for GR in both OW and DW (femoral > abdominal). Lactate release (LR) was low in DW [abdominal, 0 h: DW, 3.5 +/- 0.4; OW, 7.8 +/- 1.0 micromol/kg.min (P < 0.001); femoral, 0 h: DW, 3.1 +/- 0.3; OW, 9.0 +/- 0.9 micromol/kg.min (P < 0.001)]. LR was appropriately low for body fat mass in LW, with a brisk increase between 0 and 1.5 h. A negative correlation exists between GR (abdominal area) and insulin levels in the postabsorptive state (P < 0.0001). In conclusion, 1) the fasting lipolytic rate is associated with insulin levels; 2) OW and DW have more adipose tissue insulin resistance than LW; 3) OW and DW have a brisker lipolysis in the femoral area; and 4) in DW, higher visceral mass is associated with elevated free testosterone and FFA concentrations. Obesity in the black population is therefore characterized by a marked degree of adipose tissue lipolysis. This degree of resistance together with increasing body fat mass may predispose the obese women to developing type 2 diabetes. Once this disease is established, the onset of adipose tissue vascular insulin resistance will sustain ongoing insulin resistance, even in the presence of relative insulinopenia.
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PMID:Lactate and glycerol release from adipose tissue in lean, obese, and diabetic women from South Africa. 1144 4

Fructose is a major dietary sugar, which is elevated in the serum of diabetic humans, and is associated with metabolic syndromes important in the pathogenesis of diabetic complications. The facilitative fructose transporter, GLUT5, is expressed in insulin-sensitive tissues (skeletal muscle and adipocytes) of humans and rodents, where it mediates the uptake of substantial quantities of dietary fructose, but little is known about its regulation. We found that GLUT5 abundance and activity were compromised severely during obesity and insulin resistance in Zucker rat adipocytes. Adipocytes from young obese (fa/fa), highly insulin-responsive Zucker rats contained considerably more plasma membrane GLUT5 than those from their lean counterparts (1.8-fold per microgram membrane protein), and consequently exhibited higher fructose transport (fivefold) and metabolism (threefold) rates. Lactate production was the preferred route for fructose metabolism in these cells. As the rats aged and become more obese and insulin-resistant, adipocyte GLUT5 surface density (12-fold) and fructose transport (10-fold) and utilisation rates (threefold) fell markedly. The GLUT5 loss was more dramatic in adipocytes from obese animals, which developed a more marked insulin resistance than lean counterparts. The decline of GLUT5 levels in adipocytes from older, obese animals was not a generalised effect, and was not observed in kidney, nor was this expression pattern shared by the alpha1 subunit of the Na+/K+ ATPase. Our findings suggest that plasma membrane GLUT5 levels and thus fructose utilisation rates in adipocytes are dependent upon cellular insulin sensitivity, inferring a possible role for GLUT5 in the elevated circulating fructose observed during diabetes, and associated pathological complications.
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PMID:Fructose transport and metabolism in adipose tissue of Zucker rats: diminished GLUT5 activity during obesity and insulin resistance. 1536 82


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