Dietary milk fat globule membrane regulates JNK and PI3K/Akt pathway and ameliorates type 2 diabetes in mice induced by a high-fat diet and streptozotocin

Yuan, Qichen; Zhan, Biyuan; Du, Min; Chang, Rui; Li, Tian-ge; Mao, Xueying

doi:10.1016/j.jff.2019.103435

Cited by 21 publications

(16 citation statements)

References 48 publications

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“…[ 48 ] In our previous study, MFGM ameliorated insulin resistance through enhancing the phosphorylation of AKT in the liver and skeletal muscle of type 2 diabetes mice. [ 51 ] Similarly, in current study, maternal MFGM‐PL supplementation significantly decreased insulin levels, prevented IRS‐1 phosphorylation at Ser307 and enhanced the phosphorylation of PDK1, AKT and FoxO1 in hypothalamus of HFD offspring, indicating that MFGM‐PL ameliorated hypothalamic insulin resistance via activation of IRS‐1/PDK1/AKT/FoxO1 cascade. All these findings demonstrate that maternal MFGM‐PL supplementation benefits skeletal outcomes of HFD offspring, which is at least partially ascribed to the ameliorated hypothalamic insulin resistance and subsequently enhanced GHRH/GH/IGF‐1 axis, as shown in Figure 6 .…”

Section: Discussionsupporting

confidence: 73%

Milk Polar Lipids Supplementation to Obese Rats During Pregnancy and Lactation Benefited Skeletal Outcomes of Male Offspring

Han

Ren

et al. 2021

Molecular Nutrition Food Res

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Scope Dietary intervention to obese dams during pregnancy and lactation period provides avenues for improving metabolic profiles of the offspring. In the current study, the effects of polar lipids‐enriched milk fat globule membrane (MFGM‐PL) supplementation to obese dams during pregnancy and lactation on the skeletal outcomes of male offspring are investigated. Methods and Results MFGM‐PL is supplemented to obese rats induced by high‐fat diet during pregnancy and lactation at a dose of 400 mg kg‐1 body weight. Results show that maternal MFGM‐PL supplementation significantly ameliorates the stunted skeletal growth of male offspring at weaning. In adulthood offspring, maternal MFGM‐PL supplementation protects against high‐fat diet (HFD)‐induced bone microstructure degeneration and bone marrow adipocyte accumulation. Further investigation shows that maternal supplementation of MFGM‐PL significantly ameliorates insulin resistance and increases the mRNA expression of growth hormone releasing hormone (GHRH) in the hypothalamus of HFD offspring. The growth hormone (GH)/insulin‐like growth factor‐1 (IGF‐1) axis is subsequently enhanced in MFGM‐PL + HFD offspring, contributing to the beneficial skeletal outcomes. Conclusion The findings suggest that maternal MFGM‐PL supplementation of HFD dam during pregnancy and lactation shows desirable effects on fetal skeletal development, with lasting beneficial programming impacts on skeletal outcomes of offspring.

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Section: Discussionsupporting

confidence: 73%

Milk Polar Lipids Supplementation to Obese Rats During Pregnancy and Lactation Benefited Skeletal Outcomes of Male Offspring

Han

Ren

et al. 2021

Molecular Nutrition Food Res

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“… 41 C-Jun N-terminal kinases (JNK) play an important role in insulin target organs during the development of insulin resistance. 12 Activation of the JNK can result in insulin resistance through inhibition of IRS1. In the current study, the protein expressions of IRS1, PI3K, AKT, and JNK were detected by western blotting.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemic and Hypolipidemic Effects of Malonyl Ginsenosides from American Ginseng (Panax quinquefolius L.) on Type 2 Diabetic Mice

Liu

et al. 2021

ACS Omega

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American ginseng ( Panax quinquefolius L.) is popularly consumed as traditional herbal medicine and health food for the treatment of type 2 diabetes mellitus (T2DM). Malonyl ginsenosides (MGR) are the main natural ginsenosides in American ginseng. However, whether the malonyl ginsenosides in P. quinquefolius (PQ-MGR) possess antidiabetic effects has not been explored yet. In this study, the antidiabetic effects and the underlying mechanism of PQ-MGR in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM mice were investigated. The chemical composition was analyzed by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Our results showed that 14 malonyl ginsenosides were identified in the PQ-MGR. Among them, the content of m-Rb 1 represented about 77.4% of the total malonyl ginsenosides. After a 5-week experiment, the PQ-MGR significantly reduced the fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), nonesterified fatty acid (NEFA), alanine transaminase (ALT), and aspartate transaminase (AST) levels and improved glucose tolerance and insulin resistance. Furthermore, Western blot analysis demonstrated that the protein expressions of p-PI3K, p-AKT, p-AMPK, p-ACC, PPAR γ , and GLUT4 in the liver and skeletal muscle were significantly upregulated after PQ-MGR treatment. In contrast, the protein expressions of p-IRS1 and p-JNK were significantly downregulated. Our results revealed that PQ-MGR could ameliorate glucose and lipid metabolism and insulin resistance in T2DM via regulation of the insulin receptor substrate-1/phosphoinositide3-kinase/protein-kinase B (IRS1/PI3K/Akt) and AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathways. These findings suggest that PQ-MGR may be used as an antidiabetic candidate drug for T2DM treatment.

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“…Western blot analysis was carried out as previously described. 28 Frozen tissues were homogenized in ice-cold lysis buffer with protease inhibitor cocktail and phosphatase inhibitor cocktail. After centrifugation, protein concentrations in supernatants were determined by a bicinchoninic acid protein assay kit.…”

Section: Western Blot Analysismentioning

confidence: 99%

Supplementation of milk polar lipids to obese dams improves neurodevelopment and cognitive function in male offspring

Yuan

Gong

et al. 2021

The FASEB Journal

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Milk contains about 4% fat globules with its surface covered by polar lipids. Despite the abundant consumption of dairy products, the biological effects of dietary milk polar lipids on metabolic health have only been sparsely examined. Maternal obesity results in neurodevelopmental disorders and cognitive impairment in offspring. Considering the importance of maternal nutrition, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to dams during pregnancy and lactation on neurodevelopment and its long-term programming effects on offspring cognition were examined. Female Sprague-Dawley rats consumed 8-week control diet (CON) or high-fat diet (HFD) to induce obesity before mating. Then, female rats were fed CON or HFD with or without the supplementation of 400 mg/ kg body weight MFGM-PL during pregnancy and lactation. The offspring were fed 11-week HFD after weaning. MFGM-PL supplementation to obese dams suppressed body weight gain and hyperinsulinemia in both dams and offspring. Offspring born to obese dams displayed delayed neurological reflexes development, impaired neurogenesis before weaning, and cognitive impairment in adulthood, which were recovered by maternal MFGM-PL supplementation. Insulin resistance and aberrant brain-derived neurotrophic factor signaling were induced in the hippocampus of neonatal and adult offspring due to maternal and progeny HFD, but recovered by maternal MFGM-PL administration. This study demonstrates that maternal MFGM-PL supplementation can promote neurodevelopment and exert long-term effects against HFD-induced cognitive impairment in offspring via alleviating hippocampal insulin resistance. Hence, MFGM-PL is a promising ingredient for exerting beneficial programming effects on the brain health of offspring.

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Dietary milk fat globule membrane regulates JNK and PI3K/Akt pathway and ameliorates type 2 diabetes in mice induced by a high-fat diet and streptozotocin

Cited by 21 publications

References 48 publications

Milk Polar Lipids Supplementation to Obese Rats During Pregnancy and Lactation Benefited Skeletal Outcomes of Male Offspring

Milk Polar Lipids Supplementation to Obese Rats During Pregnancy and Lactation Benefited Skeletal Outcomes of Male Offspring

Hypoglycemic and Hypolipidemic Effects of Malonyl Ginsenosides from American Ginseng (Panax quinquefolius L.) on Type 2 Diabetic Mice

Supplementation of milk polar lipids to obese dams improves neurodevelopment and cognitive function in male offspring

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