Thermally Abused Frying Oil Potentiates Metastasis to Lung in a Murine Model of Late-Stage Breast Cancer.

Deep-frying is a popular form of food preparation used globally and throughout in the United States. Each time dietary oils are heated to deep-frying temperatures, they undergo chemical alterations that result in a new matrix of lipid structures. These lipid products include triglyceride dimers, polymers, oxidized triglycerides, and cyclic monomers, which raises nutritional concerns about associations between these lipid products and heightened health risks. Reports of associations between thermally abused frying oil and deleterious health outcomes currently exist, yet there is little information concerning the effects of thermally abused frying oil consumption and the progression of breast cancer. This study used a late-stage breast cancer murine model and in vivo bioluminescent imaging to monitor progression of metastasis of 4T1 tumor cells in animals consuming fresh soybean oil (SBO) and a thermally abused frying oil (TAFO). Bioluminescent and histologic examinations demonstrated that TAFO consumption resulted in a marked increase of metastatic lung tumor formation compared to SBO consumption. Further, in animals consuming the TAFO treatment diet, metastatic tumors in the lung displayed a 1.4-fold increase in the Ki-67 marker of cellular proliferation and RNA-sequencing analysis of the hepatic tissue revealed a dietary-induced modulation of gene expression in the liver.

Dietary licorice root supplementation reduces diet-induced weight gain, lipid deposition, and hepatic steatosis in ovariectomized mice without stimulating reproductive tissues and mammary gland.

SCOPE: We studied the impact of dietary supplementation with licorice root components on diet-induced obesity, fat accumulation, and hepatic steatosis in ovariectomized C57BL/6 mice as a menopause model. MATERIALS AND METHODS: We evaluated the molecular and physiological effects of dietary licorice root administered to ovariectomized C57BL/6 mice as root powder (LRP), extracts (LRE), or isolated isoliquiritigenin (ILQ) on reproductive (uterus and mammary gland) and nonreproductive tissues important in regulating metabolism (liver, perigonadal, perirenal, mesenteric, and subcutaneous fat). Quantitative outcome measures including body weight, fat distribution (magnetic resonance imaging), food consumption, bone density and weight (Dual-energy X-ray absorptiometry), and gene expression were assessed by the degree of restoration to the preovariectomized health state. We characterized histological (H&E and oil red O staining) and molecular properties (expression of certain disease markers) of these tissues, and correlated these with metabolic phenotype as well as blood levels of bioactives. CONCLUSION: Although LRE and ILQ provided some benefit, LRP was the most effective in reducing body weight gain, overall fat deposition, liver steatosis, and expression of hepatic lipid synthesis genes following ovariectomy. Our data demonstrate that licorice root provided improvement of multiple metabolic parameters under conditions of low estrogen and high-fat diets without stimulating reproductive tissues.

Endocytic mechanism of internalization of dietary peptide lunasin into macrophages in inflammatory condition associated with cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death in the United States. Diet influences risk factors associated with CVD and atherosclerosis, a major vascular disease that arises from inflammation. Lunasin, a peptide derived from plant foods such as soybeans, contains a unique Arg-Gly-Asp cell-adhesion motif and inhibits the pathways involved in the inflammatory cascade. The objective was to determine the mechanism by which lunasin is internalized into human THP-1 macrophages, investigate the expression of endocytic membrane proteins in inflammatory conditions and to identify the pathways involved. While lipopolysaccharide (10 nM), vitronectin (130 nM) and a combination of these two molecules enhanced lunasin uptake and increased basal αVß3 integrin expression, lunasin reduced αVß3 expression by 25.5, 26.8 and 49.2%, respectively. The pretreatment of cells with brefeldin A (71 µM), an inhibitor of protein trafficking, inhibited lunasin internalization by up to 99.8%. Lunasin increased caveolin-1 expression by up to 204.8%, but did not modulate clathrin. The pretreatment of macrophages with nystatin (54 µM), an inhibitor of caveolae-dependent endocytosis, reduced lunasin internalization. The presence of amantadine (1 mM) and amiloride (1 mM), inhibitors of clathrin-mediated endocytosis and macropinocytosis, abolished lunasin cell entry. Lunasin elicited a transient reduction in intracellular levels of Ca²âº in LPS-induced macrophages. The results suggest that internalization of lunasin into macrophages is amplified in inflammatory conditions and is primarily mediated by endocytic mechanisms that involve integrin signaling, clathrin-coated structures and macropinosomes. Lunasin may be responsible for attenuation of CVD risk factors by interacting with pathways involved in endocytosis and inflammation.

RGD-peptide lunasin inhibits Akt-mediated NF-κB activation in human macrophages through interaction with the αVß3 integrin.

SCOPE: Cardiovascular disease is the leading cause of mortality in the United States and regulation of aberrant macrophage activity under inflammatory conditions is critical for its prevention. The objective was to determine the effect of lunasin on the inhibition of Akt-mediated activation of nuclear factor-kappa B (NF-κB)-dependent markers of inflammation and to characterize the physical interaction of lunasin with the αVß3 integrin receptor in lipopolysaccharide (LPS)-induced human THP-1 macrophages. METHODS AND RESULTS: The effect of lunasin was evaluated in vitro in LPS-induced THP-1 human macrophages using immunoassays, co-immunoprecipitation (Co-IP), and fluorescence confocal microscopy. Lunasin (50 µM) reduced cyclooxygenase-2, inducible nitric oxide synthase, and NO levels by 57.9, 64.5, and 76.2%, respectively, and inhibited the activation of phosphorylated Akt and NF-κB p65 by 59.5 and 74.5%, respectively. Lunasin (50 µM) reduced exogenous release of prostaglandin E(2) and tumor necrosis factor-α by 92.5 and 94.9%, respectively. Vitronectin (10 µg/mL), an integrin ligand, increased expression of proinflammatory markers, whereas lunasin (50 µM) attenuated them. Co-IP of lunasin-treated cells confirmed direct interaction with αVß3 integrin and LC/MS/MS verified its identity. Lunasin was detected within intracellular vesicles and reduced total αVß3 intensity as observed by fluorescence microscopy. CONCLUSION: Lunasin inhibited αVß3 integrin-mediated proinflammatory markers and downregulated Akt-mediated NF-κB pathways through interaction with αVß3 integrin.

Role of dietary proteins and peptides in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States and most other countries. Therefore, a disease of such wide-ranging impact calls for the development of multiple viable strategies for prevention. Diet plays an important role in the development of the major risk factors of CVD such as low-grade systemic inflammation, hypertension, obesity, diabetes and atherosclerosis, the most significant. Thus, diet-based methods of prevention would not only be more feasible, but ultimately more cost-effective than relying on drugs to combat this condition. In recent years, peptides derived from either animal or plant sources have been found to have various bioactive properties. Nevertheless, their potential impact on inflammation and prevention of atherosclerosis has not been fully explored, particularly at the molecular level. In this review, the most current scientific information from in vitro, in vivo and clinical studies on the role of dietary proteins and peptides on CVD has been summarized and discussed.