Whey protein hydrolysates improve high‑fat‑diet‑induced obesity by modulating the brain–peripheral axis of GLP‑1 through inhibition of DPP‑4 function in mice.

Chaitra, Rai and Poornima Priyadarshini, C. G. (2023) Whey protein hydrolysates improve high‑fat‑diet‑induced obesity by modulating the brain–peripheral axis of GLP‑1 through inhibition of DPP‑4 function in mice. European Journal of Nutrition (2023) :, 62. pp. 2489-2507.

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Abstract

Obesity is a growing global health concern. Recent literature indicates a prominent role of glucagon-like peptide-1 (GLP-1) in glucose metabolism and food intake. The synergistic action of GLP-1 in the gut and brain is responsible for its satiety-inducing effect, suggesting that upregulation of active GLP-1 levels could be an alternative strategy to combat obesity. Dipeptidyl peptidase-4 (DPP-4) is an exopeptidase known to inactivate GLP-1, suggesting that its inhibition could be a crucial strategy for effectively extending the half-life of endogenous GLP-1. Peptides derived from partial hydrolysis of dietary proteins are gaining traction due to their inhibitory activity on DPP-4. Methods Whey protein hydrolysate from bovine milk (bmWPH) was produced using simulated in situ digestion, purified using RP-HPLC, and characterized for DPP-4 inhibition. The antiadipogenic and antiobesity activity of bmWPH was then studied in 3T3-L1 preadipocytes and high-fat diet-induced obesity (HFD) mice model, respectively. Results The dose-dependent inhibitory effect of bmWPH on the catalytic activity of DPP-4 was observed. Additionally, bmWPH suppressed adipogenic transcription factors and DPP-4 protein levels, leading to a negative effect on preadipocyte differentiation. In an HFD mice model, co-administration of WPH for 20 weeks downregulated adipogenic transcription factors, resulting in a concomitant reduction in whole body weight and adipose tissues. Mice fed with bmWPH also showed a marked reduction in DPP-4 levels in WAT, liver, and serum. Furthermore, HFD mice fed with bmWPH exhibited increased serum and brain GLP levels, which led to a significant decrease in food intake. Conclusion In conclusion, bmWPH reduces body weight in HFD mice by suppressing appetite through GLP-1, a satietyinducing hormone, in both the brain and peripheral circulation. This effect is achieved through modulation of both the catalytic and non-catalytic activity of DPP-4.

Item Type:	Article
Uncontrolled Keywords:	Glucagon-like peptide 1 · Dipeptidyl peptidase 4 · Gut–brain axis · Obesity · Bovine milk whey protein hydrolysate
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 09 Hormone Biochemistry
Divisions:	Molecular Nutrition
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	08 Dec 2023 09:31
Last Modified:	08 Dec 2023 09:31
URI:	http://ir.cftri.res.in/id/eprint/16844

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