Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

Liu, Yage; Tian, Yimiao; Xuan, Dong; Liu, Tianyuan; Zhang, Yueyi; Wang, Shan; Shi, Hanfen; Yin, Jun; Xu, Tao; Zhu, Ruyuan; Zhang, Yanfei; Zhao, Dongyuan; S, Gao; Wang, Xiangdong; Wang, Lili; Zhang, Dongwei

doi:10.1039/d3fo00559c

Cited by 6 publications

(5 citation statements)

References 75 publications

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“…Although metformin treatment did not reduce macrophage numbers, it did decrease their infiltration, thereby mitigating islet inflammation. This aligns with recent findings indicating metformin’s ability to inhibit islet inflammatory response and islet cell apoptosis in HFD/STZ-induced diabetic mice [ 40 ]. Importantly, both the number of macrophages and their infiltration into islets significantly decreased in the pancreas of CCB supplemented animals compared to untreated ZDF rats.…”

Section: Discussionsupporting

confidence: 92%

“…Notably, resveratrol, one of the most studied polyphenols, attenuated macrophage infiltration in pancreatic islets of T1D mice, thereby reducing beta-cell destruction [ 44 ]. More recently, it has been shown that the carotenoid lycopene may ameliorate hyperglycemia and dyslipidemia and attenuate beta-cell apoptosis by regulating the toll-like receptor 4 (TLR4)/NF-κB signaling pathway, both in islets of diabetic mice and in Min6 beta cells stimulated with the conditioned medium collected from RAW264.7 cells treated with glucose/palmitate [ 40 ]. Collectively these findings suggest that CCB treatment could prevent beta-cell loss in ZDF diabetic rats by inhibiting islet macrophage infiltration and intra-islet inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats

Gallardo-Villanueva,

Fernández-Marcelo,

Villamayor

et al. 2024

Nutrients

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The loss of functional beta-cell mass in diabetes is directly linked to the development of diabetic complications. Although dietary flavonoids have demonstrated antidiabetic properties, their potential effects on pancreatic beta-cell preservation and their synergistic benefits with antidiabetic drugs remain underexplored. We have developed a potential functional food enriched in flavonoids by combining cocoa powder and carob flour (CCB), which has shown antidiabetic effects. Here, we investigated the ability of the CCB, alone or in combination with metformin, to preserve pancreatic beta cells in an established diabetic context and their potential synergistic effect. Zucker diabetic fatty rats (ZDF) were fed a CCB-rich diet or a control diet, with or without metformin, for 12 weeks. Markers of pancreatic oxidative stress and inflammation, as well as relative beta-cell mass and beta-cell apoptosis, were analyzed. Results demonstrated that CCB feeding counteracted pancreatic oxidative stress by enhancing the antioxidant defense and reducing reactive oxygen species. Moreover, the CCB suppressed islet inflammation by preventing macrophage infiltration into islets and overproduction of pro-inflammatory cytokines, along with the inactivation of nuclear factor kappa B (NFκB). As a result, the CCB supplementation prevented beta-cell apoptosis and the loss of beta cells in ZDF diabetic animals. The observed additive effect when combining the CCB with metformin underscores its potential as an adjuvant therapy to delay the progression of type 2 diabetes.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats

Gallardo-Villanueva,

Fernández-Marcelo,

Villamayor

et al. 2024

Nutrients

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“…The criteria for diabetes in these mice were defined as fasting blood glucose levels exceeding 11.1 mM. 17 Food intake and water consumption were documented over a period of five consecutive days at 15 days post‐STZ injection. In the normal chow experiments, standard laboratory chow was provided to 6‐week‐old AKO and WT mice for 6 weeks, with body weight being recorded weekly.…”

Section: Methodsmentioning

confidence: 99%

Adipocyte‐specific FAK deletion promotes pancreatic β‐cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus

Ding,

Zheng,

Fang

et al. 2024

Clinical & Translational Med

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BackgroundWhite adipose tissue (WAT) has a key role in maintaining energy balance throughout the body, and their dysfunction take part in the regulation of diabetes mellitus. However, the internal regulatory mechanisms underlying are still unknown.Methods and resultsWe generated adipocyte‐specific FAK KO (FAK‐AKO) mice and investigated their phenotype. The cascade of adipocyte, macrophage in adipocyte tissues, and pancreatic β‐cells were proposed in FAK‐AKO mice and validated by cell line studies using 3T3‐L1, Raw264.7 and Min6. The FAK‐AKO mice exhibited glucose intolerance, reduced adipose tissue mass and increased apoptosis, lipolysis and inflammatory response in adipose tissue. We further demonstrate that adipocyte FAK deletion increases β cell apoptosis and inflammatory infiltrates into islets, which is potentiated if mice were treated with STZ. In the STZ‐induced diabetes model, FAK AKO mice exhibit less serum insulin content and pancreatic β cell area. Moreover, serum pro‐inflammatory factors increased and insulin levels decreased after glucose stimulation in FAK AKO mice. In a parallel vitro experiment, knockdown or inhibition of FAK during differentiation also increased apoptosis, lipolysis and inflammatory in 3T3‐L1 adipocytes, whereas the opposite was observed upon overexpression of FAK. Moreover, coculturing LPS‐treated RAW264.7 macrophages with knockdown FAK of 3T3‐L1 adipocytes increased macrophage pro‐inflammatory response. Furthermore, conditioned medium from above stimulated Min6 cells apoptosis (with or without STZ), whereas the opposite was observed upon overexpression of FAK. Mechanistically, FAK protein interact with TRAF6 in adipocytes and knockdown or inhibition of FAK activated TRAF6/TAK1/NF‐κB signaling, which exacerbates inflammation of adipocytes themselves.ConclusionAdipocyte FAK deletion promotes both adipocyte apoptosis and adipose tissue inflammation. Pro‐inflammatory factors released by the FAK‐null adipose tissue further trigger apoptosis in pancreatic islets induced by the administration of STZ, thereby exacerbating the diabetes mellitus. This study reveals a link between FAK‐mediated adipose inflammation and diabetes mellitus, a mechanism that has not been previously recognized.

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“…Lycopene is also an inhibitor of NF-κB, which is a critical transcription factor mediating the expression of multiple inflammatory factors, including TNF-α, IL-1β, COX2, and IL-6 [117]. The inhibitory effects of lycopene on the NF-κB pathway could be mediated via the blockade of the MAPK and TLR4 pathways [118,119]. In addition, excessive ROS production could exacerbate the generation of pro-inflammatory cytokines and chemokines via triggering the PKC, NLRP3, TLR4, NF-κB, and MAPK pathways [16,120].…”

Section: Improvement In Inflammatory Response and Immune Functionmentioning

confidence: 99%

Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions

Li,

Tang,

Peng

et al. 2024

Antioxidants

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Aflatoxin (AFT) contamination poses a significant global public health and safety concern, prompting widespread apprehension. Of the various AFTs, aflatoxin B1 (AFB1) stands out for its pronounced toxicity and its association with a spectrum of chronic ailments, including cardiovascular disease, neurodegenerative disorders, and cancer. Lycopene, a lipid-soluble natural carotenoid, has emerged as a potential mitigator of the deleterious effects induced by AFB1 exposure, spanning cardiac injury, hepatotoxicity, nephrotoxicity, intestinal damage, and reproductive impairment. This protective mechanism operates by reducing oxidative stress, inflammation, and lipid peroxidation, and activating the mitochondrial apoptotic pathway, facilitating the activation of mitochondrial biogenesis, the endogenous antioxidant system, and the nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH-associated protein 1 (KEAP1) and peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) pathways, as well as regulating the activities of cytochrome P450 (CYP450) enzymes. This review provides an overview of the protective effects of lycopene against AFB1 exposure-induced toxicity and the underlying molecular mechanisms. Furthermore, it explores the safety profile and potential clinical applications of lycopene. The present review underscores lycopene’s potential as a promising detoxification agent against AFB1 exposure, with the intent to stimulate further research and practical utilization in this domain.

show abstract

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

Abstract: Inflammation of the pancreatic islets triggers β cells dysfunction and type 2 diabetes mellitus (T2DM) onset. While dietary lycopene consumption contributes to protect against T2DM in animal studies, the potential...

Cited by 6 publications

References 75 publications

Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats

Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats

Adipocyte‐specific FAK deletion promotes pancreatic β‐cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus

Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions

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