Abstract
Background and Aims: The increasing prevalence and absence of effective global treatment for metabolic syndrome (MetS) are alarming given the potential progression to severe non-communicable disorders such as type 2 diabetes and nonalcoholic fatty liver disease. The purpose of this study was to investigate the regulatory role of glycomacropeptide (GMP), a powerful milk peptide, in insulin resistance and liver dysmetabolism, two central MetS conditions. Materials and Methods: C57BL/6 male mice were fed a chow (Ctrl), high-fat, high-sucrose (HFHS) diet or HFHS diet along with GMP (200 mg/kg/day) administered by gavage for 12 weeks. Results: GMP lowered plasma insulin levels (in response to oral glucose tolerance test) and HOMA-IR index, indicating a more elevated systemic insulin sensitivity. GMP was also able to decrease oxidative stress and inflammation in the circulation as reflected by the decline of malondialdehyde, F2 isoprostanes and lipopolysaccharide. In the liver, GMP raised the protein expression of the endogenous anti-oxidative enzyme GPx involving the NRF2 signaling pathway. Moreover, the administration of GMP reduced the gene expression of hepatic pro-inflammatory COX-2, TNF-α and IL-6 via inactivation of the TLR4/NF-κB signaling pathway. Finally, GMP improved hepatic insulin sensitization given the modulation of AKT, p38 MAPK and SAPK/JNK activities, thereby restoring liver homeostasis as revealed by enhanced fatty acid β-oxidation, reduced lipogenesis and gluconeogenesis. Conclusions: Our study provides evidence that GMP represents a promising dietary nutraceutical in view of its beneficial regulation of systemic insulin resistance and hepatic insulin signaling pathway, likely via its powerful antioxidant and anti-inflammatory properties.
Highlights
The impact of bovine milk consumption on human health has always sparked fierce debate, which has prompted many scientists to reassess its attributes [1,2]
Mice fed a regular chow (Ctrl) or a HFHS diet did not differ in their energy intake (Figure 1A), but as expected, HFHS diet led to a significant increase in total body weight gain (Figure 1B)
The present work highlights the beneficial modulatory effects of GMP, a bioactive milk peptide, on systemic and liver abnormalities induced by a HFHS diet in mice
Summary
The impact of bovine milk consumption on human health has always sparked fierce debate, which has prompted many scientists to reassess its attributes [1,2]. Biomedicines 2021, 9, 1140 milk consumption with the reduced risk of developing obesity, metabolic syndrome (MetS), diabetes and cardiovascular diseases [2,5]. There is a renewed interest in valuable bioactive peptides derived from major human and bovine milk proteins given their high potential in magnifying health benefits for neonates, infants, adolescents and adults [6,7]. They exert remarkable protective effects on cardiometabolic health [6,8].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call