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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 3 937-941
Copyright © 1999 by The Endocrine Society

From the Clinical Research Centers

Hyperenterostatinemia in Premenopausal Obese Women1

C. Prasad, M. Imamura, C. Debata, F. Svec, N. Sumar and J. Hermon-Taylor

Louisiana State University-Tulane General Clinical Research Center and the Obesity Research Program, Section of Endocrinology, Department of Medicine (C.P., M.I., C.D., F.S.), Louisiana State University Medical Center, New Orleans, Louisiana 70112; and the Department of Surgery (N.S., J.H.-T.), St. George’s Hospital Medical School, London SW17 ORE, United Kingdom

Address all correspondence and requests for reprints to: Dr. Chandan Prasad, Section of Endocrinology, Department of Medicine, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112. E-mail: cprasa{at}lsumc.edu


   Abstract
Top
 Abstract
Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 
Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of procolipase after tryptic cleavage and belong to the family of gut-brain peptides. Although enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined. To determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR and APGPR levels were measured in 38 overnight-fasted subjects (body mass index, 17.9–54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of lean subjects was significantly lower than that in obese subjects [lean = 603 ± 86 nmol/L (n = 17); obese, 1516 ± 227 nmol/L (n = 21); P = 0.0023]. In addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was significantly higher in lean than in obese subjects [lean, 1.71 ± 0.24 (n = 17); obese, 1.05 ± 0.14 (n = 21); P = 0.0332]. The results of these studies show hyperenterostatinemia in obesity and a diminution in enterostatin secretion after satiety.


   Introduction
Top
 Abstract
 Introduction
Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 
OBESITY plays a major role in the pathophysiology of cardiovascular disease, cancer, and diabetes (1, 2, 3, 4, 5). As prolonged consumption of a diet rich in fat elevates the risk of obesity (6, 7, 8, 9, 10, 11), it is of interest to understand the factors controlling fat intake. Of the many known endogenous modulators of dietary fat preference (e.g. serotonin, galanin, arginine vasopressin, and cyclo-His-Pro), enterostatin is the most selective (12, 13, 14). Enterostatin is a pentapeptide generated by the action of trypsin on procolipase in the intestinal lumen (15, 16). Its structure is highly conserved in evolution, with an amino acid sequence of XPXPR (17, 18). Three enterostatin sequences, Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR), have been studied extensively and shown to be almost equally effective in their ability to decrease dietary fat preference (19, 20, 21). However, until recently, due to the lack of a sensitive assay, it has not been possible to explore the roles of endogenous enterostatins in human obesity and/or appetite behavior. Recent development of specific enzyme-linked immunosorbent assays (ELISAs) for APGPR/VPGPR (22) and VPDPR (23) has enabled us to examine the changes in these three forms of enterostatins in human obesity.


   Experimental Subjects
Top
 Abstract
 Introduction
 Experimental Subjects
Materials and Methods
 Results
 Discussion
 References
 
The study population comprised 38 healthy premenopausal women. Their age, race, and body mass index (BMI) are shown in Table 1Go. Women were recruited from the medical clinics of Louisiana State University Medical Center (New Orleans, LA), the Medical Center of Louisiana (New Orleans, LA), and the general population of the New Orleans area. All recruitment plans and protocols were approved by the Institutional Review Board of Louisiana State University Medical Center. Pertinent clinical data (weight, height, waist circumference, hip circumference, etc.) were recorded for each volunteer. For some comparisons, the subjects were divided into lean (BMI, <=25) and obese (BMI, >25) subgroups.


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  		Table 1. Characteristics of the study population

 

   Materials and Methods
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
Results
 Discussion
 References
 
Subjects were asked to report to the General Clinical Research Center before 2100 h on the evening before the study. On arrival at the General Clinical Research Center, they were shown the location of the bathroom and the nurses’ station and were examined. Starting at 2300 h, the volunteers were asked to remain in bed and not to consume any food. They were allowed water but no caloric beverages. At 2300 h, an indwelling heparin lock access to a vein in the arm was secured by one of the nurses. The volunteers were asked to sleep immediately thereafter. At 2300 h, the nursing staff removed 5-mL samples of blood through the iv line, and the samples were centrifuged and processed for the analysis of enterostatins. At exactly noon, a 1000-calorie mixed meal was given to volunteers, and they were asked to eat their meals within 20 min. Thereafter, trays were removed, and the volunteers were asked to relax as before. At 1300 h, the nursing staff removed another 5-mL sample of blood through the iv line, and the samples were processed as before. Serum samples were stored frozen at -70 C until assayed for the enterostatins APGPR and VPDPR.

ELISA procedures using anti-VPDPR (23) and anti-APGPR (22) antibodies were previously described. The VPDPR antibody used in this assay has been shown to be highly specific for VPDPR, with no significant (<0.125%) affinity for a variety of related peptides, including APGPR and VPGPR. In contrast, the APGPR antibody exhibits significant affinity for VPGPR. Neither anti-VPDPR nor anti-APGPR antibody had any cross-reactivity with large mol wt proteins associated with serum albumin preparations from rabbit, bovine, goat, or human. To inhibit proteolytic degradation of enterostatins during the assay, two protease inhibitors (final concentrations, 1 mmol/L diprotein A and 0.1 mmol/L captopril) were added to the serum samples before ELISA. The intraassay/interassay coefficients of variation for VPDPR and APGPR assays were 5.6%/9.8% and 9.5%/8.9%, respectively. Under the conditions described in this assay for VPDPR, the ID50 of the antigen-antibody reaction was achieved at 10 ng/well or 0.34 µmol/L; the limit of detection was about 300 pg/well or 10.2 nmol/L. The useful range of the standard curve, however, extended up to 20 ng/well or 0.68 µmol/L. For the APGPR assay, the ID50 of the antigen-antibody reaction was achieved at 20 ng/well or 0.68 µmol/L; the limit of detection was about 550 pg/well or 18.7 nmol/L. The useful range of the standard curve for the APGPR assay, however, extended up to 50 ng/well or 1.70 µmol/L.

To extract enterostatins, serum was mixed with 9 vol methanol, and the mixture was stored over ice for 30–60 min and then centrifuged at 11,000 x g for 10 min at 4 C. The clear supernatant was lyophilized to dryness and then reconstituted appropriately for ELISA or chromatography. To ascertain the size of serum VPDPR-like immunoreactivity (VPDPR-LI) and APGPR-LI, gel filtration chromatography was performed using Sephadex G-25 (50 x 1.0 cm; 39.3 mL; fractionation range for globular proteins, 1–5 kDa) column. Lyophilized methanol-extracted serum reconstituted in a minimal volume of distilled water was loaded on columns equilibrated with buffer A (10 mmol/L NH4HCO3). A detailed description of the conditions of chromatography on each column is presented in the figure legends. Each fraction collected from the columns was subjected to ELISA to measure enterostatin-like immunoreactivity using rabbit antipeptide antibodies. The peaks representing VPDPR-LI/APGPR-LI on Sephadex G-25 were pooled, evaporated to dryness, and reconstituted in 1.0 mL distilled water, and a 0.15-mL portion was applied to a high performance liquid chromatography (HPLC) column (Novo-pack C18 60A; 4 µm; 3.9 x 300 mm; 40 C). The column was eluted (0.5 mL/min) using a linear gradient of acetonitrile (0.1–35%) in 0.1% trifluoroacetic acid and 0.05% triethylamine. Each fraction was subjected to ELISA to measure enterostatin-like immunoreactivity using rabbit anti-peptide antibodies.

Data were analyzed using the Macintosh INSTAT program. The data were first tested for normal distribution using the Shapiro-Wilk test for normalcy. Enterostatin values in lean and obese subjects were not normally distributed; therefore, the Mann-Whitney U test was used for comparison. The relationships between BMI and enterostatins were analyzed by regression analysis.


   Results
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
Discussion
 References
 
We have examined human serum samples for the presence of enterostatin-like immunoreactivity by ELISA using two antibodies: rabbit anti-VPDPR and rabbit anti-APGPR. The first antibody recognizes VPDPR, but not APGPR or VPGPR, and the second antibody recognizes both APGPR and VPGPR, but not VPDPR. The data presented in Fig. 1Go examines three characteristics of VPDPR-LI (left panel) and APGPR-LI (right panel) from human sera from lean and obese subjects. These include immunoidentity between authentic peptide and endogenous immunoreactivity (top panel), Sephadex G-25 chromatographic (middle panel), and HPLC (bottom panel) profiles. Both lean and obese human sera had a single peak of immunoreactivity associated with VPDPR-LI and APGPR-LI. The data presented in Fig. 1Go (top panel) show that the addition of synthetic peptides to the assay well led to a dose-dependent decrement in the binding of antibody to the peptide attached to the well and, therefore, to a decrease in A450 nm. The addition of human serum to the assay well reduced A450 nm in proportion to its peptide content in a manner parallel to the synthetic peptide. These data suggest an immunoidentity between brain enterostatin-like immunoreactivity and synthetic VPDPR and APGPR. Further characterization of human serum VPDPR-LI/APGPR-LI by gel filtration chromatography on Sephadex G-25 (Fig. 1Go, center panel) revealed that although serum APGPR-LI behaved identically to synthetic APGPR, the VPDPR-LI eluted later than VPDPR. These data suggest that although VPDPR-LI and VPDPR share immunoidentity, VPDPR-LI may be a slightly smaller peptide. The material eluting from the Sephadex G-25 column was concentrated and further fractionated by HPLC. The data presented in Fig. 1Go (bottom panel) show that although APGPR-LI had same elution time as synthetic APGPR, the serum VPDPR-LI had a much shorter elution time (5–6 min) compared to authentic VPDPR (26 min). In conclusion, human serum APGPR-LI is similar to synthetic APGPR; however, serum VPDPR-LI is not VPDPR, VPGPR, or APGPR, but a peptide similar to VPDPR.



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  		Figure 1. Top panel, The analysis of immunoidentity between methanol-extracted human serum and synthetic VPDPR (left) or APGPR (right). Middle panel, A comparison of the chromatographic profile of methanol-extracted human serum and synthetic VPDPR (left) or APGPR (right) on a Sephadex G-25 column. A, A 1-mL sample was loaded on the column (50 x 1.0 cm; 39.3 mL), and the column was eluted with 10 mmol/L NH4HCO3 at a rate of about 5 min/1-mL fraction. Each fraction was assayed for VPDPR-LI and APGPR-LI by ELISA. Bottom panel, HPLC elution profile of VPDPR-LI (left) and APGPR-LI (right) from human serum. Human serum was extracted with 90% methanol, fractionated on Sephadex G-25, and then loaded on the HPLC column. Each fraction was assayed for VPDPR-LI and APGPR-LI by ELISA.

 
The characteristics of lean and obese subjects with regard to race, age, BMI, weight, height, body fat, and waist are summarized in Table 1Go. The two groups were similar in age and height, but not in other attributes. Table 2Go shows VPDPR and APGPR levels in lean and obese women before and after a meal as well as the ratio of postmeal to fasting enterostatin levels. Both fasting (P = 0.0023) and postmeal (P = 0.0196) VPDPR, but not APGPR, levels were higher in obese compared with lean women. In contrast, the ratio of postmeal to fasting levels of APGPR, but not VPDPR was significantly elevated in lean compared with obese women.


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  		Table 2. Enterostatin levels in premenopausal lean and obese women

 
In fasting subjects, VPDPR (Fig. 2Go, top left) correlated strongly (r2 = 0.516; P < 0.005) with BMI; the change in VPDPR (Fig. 2Go, top right) after the meal (postmeal to fasting ratio) did not exhibit a meaningful relationship to BMI (r2 = 0.083; P < 0.05). On the other hand, although there was no significant relationship between fasting APGPR (Fig. 2Go, bottom left) and BMI (r2 = 0.048; P < 0.05), the postmeal to fasting ratio (Fig. 2Go, bottom right) decreased with increasing BMI (r2 = 0.163; P > 0.10).



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  		Figure 2. Relationship between BMI and serum fasting VPDPR (upper left), postmeal/fasting serum VPDPR (upper right), serum fasting APGPR (bottom left), and postmeal/fasting serum APGPR (bottom right).

 

   Discussion
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
References
 
This study examines the relationship between BMI, a measure of obesity, and serum levels of two enterostatins (VPDPR and APGPR) in fasted women before and after a standardized meal. We found that 1) both VPDPR and APGPR were present in the serum of premenopausal wo-men; 2) fasting serum VPDPR, but not APGPR, increased with increasing BMI; and 3) although there was a diminu-tion in the increase in serum APGPR after a meal with increasing obesity, a meal did not affect serum VPDPR levels.

This is the first report of simultaneous measurement and characterization of enterostatin (APGPR and VPDPR)-like immunoreactivities in human serum. The molar concentrations of two enterostatins observed in this study were several hundred to a thousand times higher than those of other biologically active peptides (e.g. neuropeptide Y, somatostatin, vasoactive intestinal peptide, and TRH) in human blood (24, 25, 26, 27). In contrast, human cerebrospinal fluid contained low levels of VPDPR-LI and no measurable APGPR-LI (28).

Enterostatins are selective inhibitors of appetite, particularly of fat intake (15, 16, 19, 20, 21); therefore, one would expect decreased levels of enterostatin in the obese. In contrast, we observed an increase in one of the two enterostatins (VPDPR) with increasing BMI. Consumption of a meal should signal satiety, and therefore, serum levels of enterostatin, a peptide known to elicit satiety in rodents, would be expected to rise after a meal. Consistent with this hypothesis, we observed that the meal-induced rise in serum APGPR was higher in lean (satiated) subjects and lower in obese (nonsatiated) subjects. In summary, these data point to two separate, but related, defects in enterostatin physiology in obesity. First, an aberrant increase in enterostatin (VPDPR) synthesis/secretion in obesity, and second, a diminution in the meal-induced increase in enterostatin (APGPR) with increasing obesity. Hyperenterostatinemia in obesity is probably secondary to enterostatin resistance; therefore, the regulatory system is producing more enterostatin to counteract the resistance. This is very similar to hyperinsulinemia and hyperleptine mia in obesity. The diminution in the meal-induced secretion of enterostatin in obesity suggests a delay in the appearance of satiety, leading to increased caloric intake.

At this time we can only speculate about the origin or molecular mechanism underlying differences in the meal-induced rise in the enterostatin APGPR. It may be due to differences between lean and obese subjects in the clearance of circulating enterostatin or secretion from gut, an area known to be richly endowed with APGPR (29, 30). It is also possible that the gene(s) responsible for enterostatin synthesis may be differentially expressed in lean and obese subjects. Enterostatin is currently thought to be exclusively derived from tryptic cleavage of colipase gene product, which is abundantly expressed in many peripheral tissues (31). However, whether there is a separate gene for enterostatin remains to be determined.

In humans, the role of enterostatin in body weight regulation is unclear. In rats, however, enterostatin decreases body weight by decreasing fat-calorie intake (32) and increasing the sympathetic firing rate of the nerves in interscapular brown adipose tissue (33, 34). If this were the case for humans, there should have been a decrease in serum enterostatin levels with increasing BMI, but our results were just the opposite. One explanation may be reduced receptor sensitivity to enterostatin in obese women. Conversely, higher enterostatin levels in obese subjects may reflect a compensatory increase in the secretion/synthesis of enterostatin due to enterostatin resistance at target tissues.


   Acknowledgments
 
The authors thank Ms. Anne Compliment for her superb and timely editorial assistance.


   Footnotes
 
1 This work was supported in part by grants from the Air Force Office of Scientific Research (DEPSCoR-94-NL-102), Board of Regents, State of Louisiana, and the Catherine Vernice and Vincent Charles Vernice Research Fund in Endocrinology. Back

Received November 4, 1998.

Revised December 9, 1998.

Accepted December 14, 1998.


   References
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 

  1. Stevens J. 1995 Obesity, fat patterning and cardiovascular risk. Adv Exp Med Biol. 369:21–27.[Medline]
  2. Schindler AE. 1997 Obesity and cancer risk in women. Arch Gynecol Obstet. 261:21–24.[Medline]
  3. Pujol P, Galtier-Dereure F, Bringer J. 1997 Obesity and breast cancer risk. Hum Reprod. 12(Suppl 1):116–125.
  4. Cleary MP, Maihle NJ. 1997 The role of body mass index in the relative risk of developing premenopausal vs. postmenopausal breast cancer. Proc Soc Exp Biol Med. 216:28–43.[Abstract]
  5. Amanti M, Schumann L. 1998 Coronary artery disease: a link between hypertension, diabetes mellitus, hyperlipidemia, and obesity. J Am Acad Nurse Pract. 10:77–81.[Medline]
  6. Lichtenstein AH, Kennedy E, Barrier P, et al. 1998 Dietary fat consumption and health. Nutr Rev. 56:S3–28.
  7. Roberts SB, Pi-Sunyer FX, Dreher M, et al. 1998 Physiology of fat replacement and fat reduction: effects of dietary fat and fat substitutes on energy regulation. Nutr Rev. 56:S29–41.
  8. Reed DR, Bachmanov AA, Beauchamp GK, Tordoff MG, Price RA. 1997 Heritable variation in food preferences and their contribution to obesity. Behav Genet. 27:373–387.[CrossRef][Medline]
  9. Lawton CL, Blundell JE. 1998 The role of reduced fat diets and fat substitutes in the regulation of energy and fat intake and body weight. Curr Opin Lipidol. 9:41–45.[CrossRef][Medline]
  10. Willett WC. 1998 Is dietary fat a major determinant of body fat?. Am J Clin Nutr. 67(Suppl 3):556S–562S.
  11. Seidell JC. 1998 Dietary fat and obesity: an epidemiologic perspective. Am J Clin Nutr. 67(Suppl 3):546S–550S.
  12. Bray GA. 1992 Peptides affect the intake of specific nutrients and the sympathetic nervous system. Am J Clin Nutr. 55(Suppl 1):265S–271S.
  13. Blundell JE, Lawton CL. 1995 Serotonin and dietary fat intake: effects of dexfenfluramine. Metabolism. 44(Suppl 2):33–37.
  14. Blundell JE, Lawton CL, Halford JC. 1995 Serotonin, eating behavior, and fat intake. Obesity Res. 3(Suppl 4):471S–476S.
  15. Sorhede M, Mei J, Erlanson-Albertsson C. 1993 Enterostatin: a gut-brain peptide regulating fat intake in rat. J Physiol. 87:273–275.
  16. Erlanson-Albertsson C. 1992 Enterostatin: the pancreatic procolipase activation peptide–a signal for regulation of fat intake. Nutr Rev. 50:307–310.[Medline]
  17. Erlanson-Albertsson C. 1994 Pancreatic lipase, colipase and enterostatin–a lipolytic triad. In: Mackness MI, Clerc M, eds. Esterases, lipases and phospholipases: from structure to clinical significance. New York: Plenum Press; 159–168.
  18. Erlanson-Albertsson C. 1992 Pancreatic colipase. Structural and physiological aspects. Biochim Biophys Acta. 1125:1–7.[Medline]
  19. Erlanson-Albertsson C, Mei J, Okada S, York D, Bray GA. 1991 Pancreatic procolipase propeptide, enterostatin, specifically inhibits fat intake. Physiol Behav. 49:1191–1194.[CrossRef][Medline]
  20. Okada S, York DA, Bray GA. Erlanson-Albertsson C. 1991 Enterostatin (Val-Pro-Asp-Pro-Arg), the activation peptide of procolipase, selectively reduces fat intake. Physiol Behav. 49:1185–1189.[CrossRef][Medline]
  21. Shargill NS, Tsujii S, Bray GA. Erlanson-Albertsson C. 1991 Enterostatin suppresses food intake following injection into the third ventricle of rats. Brain Res. 544:137–140.[CrossRef][Medline]
  22. Bowyer RC, Jehanli AMT, G. Patel G, Hermon-Taylor J. 1991 Development of enzymelinked immunosorbent assay for free human procolipase activation peptide (APGPR). Clin Chim Acta. 200:137–152.[CrossRef][Medline]
  23. Mizuma H, Imamura M, Tiemann WE, Prasad C. 1995 Biology of enterostatin. II. Development of enzyme-linked immunosorbentassay (ELISA) for enterostatin (Val-Pro-Asp-Pro-Arg), the procolipase activation peptide. Biochem Biophys Res Commun. 215:227–234.[Medline]
  24. Strazzulla G, Guazzelli R, Romano S, et al. 1990 Circadian variations of plasma somatostatin levels in healthy subjects. Chronobiologia. 17:219–225.[Medline]
  25. Azukizawa M, Mitsuma T, Ota M, et al. 1980 Fluctuation of the plasma TRH level in normal subjects in a 4-hour observation period. Endocrinol Jpn. 27:371–374.[Medline]
  26. Manfredi R, Vezzadini P, Costigliola P, et al. 1993 Elevated plasma levels of vasoactive intestinal peptide in AIDS patients with refractory idiopathic diarrhoea. Effects of treatment with octreotide. AIDS. 7:223–226.[Medline]
  27. Nystrom F, Nilsson P, Olsson AG, et al. 1996 A population study of plasma neuropeptide Y: correlations with components of the metabolic syndrome. Blood Pressure. 5:349–353.[Medline]
  28. Imamura M, Sumar N, Hermon-Taylor J, et al. 1998 Distribution and characterization of enterostatin-like immunoreactivity in human cerebrospinal fluid. Peptides. 19:1385–1391.[Medline]
  29. Sorhede M, Erlanson-Albertsson C, Mei J, Nevalainen T, Aho A, Sundler F. 1996 Enterostatin in gut endocrine cells–immunocytochemical evidence. Peptides. 17:609–614.[CrossRef][Medline]
  30. Sorhede M, Mulder H, Mei J, Sundler F, Erlanson-Albertsson C. 1996 Procolipase is produced in the rat stomach–a novel source of enterostatin. Biochim Biophys Acta. 1301:207–212.[Medline]
  31. Okada S, York DA, Bray GA. 1993 Procolipase mRNA: tissue localization and effects of diet and adrenalectomy. Biochem J. 292:787–789.
  32. Lin L, Chen J, York DA. 1997 Chronic ICV enterostatin preferentially reduced fat intake and lowered body weight. Peptides. 18:657–661.[CrossRef][Medline]
  33. Nagase H, Bray GA, York DA. 1996 Effect of galanin and enterostatin on sympathetic nerve activity to interscapular brown adipose tissue. Brain Res. 709:44–50.[CrossRef][Medline]
  34. Tian Q, Nagase H, York DA, Bray GA. 1994 Vagal-central nervous system interactions modulate the feeding response to peripheral enterostatin. Obesity Res. 2:527–534.[Medline]




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