Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery

David E. Cummings, M.D., David S. Weigle, M.D., R. Scott Frayo, B.S., Patricia A. Breen, B.S.N., Marina K. Ma, E. Patchen Dellinger, M.D., and Jonathan Q. Purnell, M.D.

ABSTRACT

Background Weight loss causes changes in appetite and energy expenditure that promote weight regain. Ghrelin is a hormone that increases food intake in rodents and humans. If circulating ghrelin participates in the adaptive response to weight loss, its levels should rise with dieting. Because ghrelin is produced primarily by the stomach, weight loss after gastric bypass surgery may be accompanied by impaired ghrelin secretion.

Methods We determined the 24-hour plasma ghrelin profiles, body composition, insulin levels, leptin levels, and insulin sensitivity in 13 obese subjects before and after a six-month dietary program for weight loss. The 24-hour ghrelin profiles were also determined in 5 subjects who had lost weight after gastric bypass and 10 normal-weight controls; 5 of the 13 obese subjects who participated in the dietary program were matched to the subjects in the gastric-bypass group and served as obese controls.

Results Plasma ghrelin levels rose sharply shortly before and fell shortly after every meal. A diet-induced weight loss of 17 percent of initial body weight was associated with a 24 percent increase in the area under the curve for the 24-hour ghrelin profile (P=0.006). In contrast, despite a 36 percent weight loss after gastric bypass, the area under the curve for the ghrelin profile in the gastric-bypass group was 77 percent lower than in normal-weight controls (P<0.001) and 72 percent lower than in matched obese controls (P=0.01). The normal, meal-related fluctuations and diurnal rhythm of the ghrelin level were absent after gastric bypass.

Conclusions The increase in the plasma ghrelin level with diet-induced weight loss is consistent with the hypothesis that ghrelin has a role in the long-term regulation of body weight. Gastric bypass is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of the procedure.


Source Information

From the Departments of Medicine (D.E.C., D.S.W., R.S.F., P.A.B., M.K.M.) and Surgery (E.P.D.), University of Washington; the Veterans Affairs Puget Sound Health Care System (D.E.C., R.S.F., M.K.M.); the Harborview Medical Center (D.S.W., P.A.B.); and University Hospital (E.P.D.) — all in Seattle; and the Department of Medicine, Oregon Health and Science University, Portland (J.Q.P.).

Address reprint requests to Dr. Cummings at the Veterans Affairs Puget Sound Health Care System, Seattle Div., 1660 S. Columbian Way, S-111-Endo, Seattle, WA 98108, or at davidec~u.washington.edu.

https://content.nejm.org/cgi/conten...act/346/21/1623

Two hormones in the stomach that can reduce the amount of ghrelin we produce are leptin and PYY (peptide YY3-36) Some obese people are resistant to leptin. This article refers to a study done about PYY....very interesting.


Inhibition of Food Intake in Obese Subjects by Peptide YY3–36

Rachel L. Batterham, M.B., B.S., Mark A. Cohen, M.B., Ch.B., Sandra M. Ellis, B.Sc., Carel W. Le Roux, M.B., Ch.B., Dominic J. Withers, M.B., B.S., Ph.D., Gary S. Frost, Ph.D., Mohammad A. Ghatei, Ph.D., and Stephen R. Bloom, M.D., D.Sc.

Perspective
by Korner, J.
PubMed Citation
ABSTRACT

Background The gut hormone fragment peptide YY3–36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.

Methods We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.

Results Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [±SE] fasting PYY levels were 10.2±0.7 pmol per liter in the obese group and 16.9±0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r = –0.84, P<0.001).

Conclusions We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis (creation) of obesity.



Source Information

From the Department of Metabolic Medicine, Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Rd., London W12 0NN, United Kingdom.

PYY deficiency?

HA!

Dietary protein and fat deficiency I say!

We need a study that correlates PYY production with protein and fat intake.

GooGoo,

Thanks for your post. Do you what year this study was done?