Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery

Abstract

Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.

Decreased circulating dipeptidyl peptidase-4 activity after short-term intensive insulin therapy predicts clinical outcomes in patients with newly diagnosed type 2 diabetes

“…The concentration of circulating DPP-4 is associated with both visceral adipose tissue volume and adipocyte size, and increases concomitantly with the obesity progression, the development of insulin resistance, and the worsening of glucose metabolic abnormalities ( 26 ). In addition, circulating DPP-4 levels have been shown to increase in patients with non-alcoholic fatty liver disease, and are positively correlated with liver enzymes ( 29 ). Rodent studies indicated that hepatic overexpression of DPP-4 contributes to elevated plasma DPP-4 levels, mediating the crosstalk between liver and adipose tissue by activating macrophages and triggering inflammation ( 30 , 31 ).…”

“…The shedding of DPP-4 from the cell surface increases in high glucose conditions ( 32 ), which may contribute to the increased circulating DPP-4 observed in patients with type 2 diabetes. Several treatments for hyperglycemia, including SGLT-2 inhibitors ( 30 ), metformin ( 20 ), calorie restriction ( 33 ), and bariatric surgery ( 29 ), can reduce circulating DPP-4 levels. However, there is relatively little research on the role of circulating DPP-4 activity as an indicator of treatment response.…”

Management and interplay of Type 2 Diabetes Mellitus with obesity

“…(50) DPP-4 inhibitors typically do not affect weight, while they have been associated with a small amount of weight loss . (51) 4. SGLT2 Inhibitors: A class of medications used to decrease blood sugar called sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the reabsorption of glucose by the kidneys (52) The renal tubules reabsorb all filtered glucose, and SGLT2 is responsible for more than 90% of this process.…”

Reappraising the role of the vagus nerve in GLP‐1‐mediated regulation of eating

“…Importantly, this only occurs with supraphysiological GLP‐1 concentrations that are 4–5 times higher than those reported after meals. Such elevated levels can be reached in animals that have undergone bariatric surgery (Peterli et al, 2012), as a result of the increased unabsorbed nutrients reaching the distal L‐cells (Larraufie et al, 2019) and/or reduced dipeptidyl peptidase 4 expression (Herz et al, 2021).…”