Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation

Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet-fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosisopen0

Toxicological evaluation of peroxisome proliferators. Further cellular and molecular aspects.

International audienc

Prophylaxis of Non-communicable Diseases: Why fruits and vegetables may be better chemopreventive agents than dietary supplements based on isolated phytochemicals?

The World Health Organization (WHO) report from 2014 documented that non-communicable so-called civilization diseases such as cardiovascular disease, chronic respiratory diseases, cancer or type 2 diabetes are responsible for over 50% of all premature deaths in the world. Research carried out over the past 20 years has provided data suggesting that diet is an essential factor influencing the risk of development of these diseases. The increasing knowledge on chemopreventive properties of certain food ingredients, in particular, those of plant origin, opened the discussion on the possibility to use edible plants or their active components in the prevention of these chronic diseases. Health-promoting properties of plant foods are associated with the presence of secondary metabolites that can affect many biological mechanisms of critical importance to the proper functioning of the human organism. Particularly, there have been numerous investigations indicating strong physiological effects of bioactive plant phenols belonging to the flavonoid family. These observations initiated mass production of dietary supplements containing flavonoids commercialized under the name antioxidants, even if their chemical properties did not justify such a term. However, epidemiological studies revealed that isolated bioactive phytochemicals are not as effective as fruits and vegetables containing these substances whereas they are of interest of the functional food industry. In this paper, the critical assessment of reasons for this turn of events has been attempted and the concept of food synergy has been suggested as a future strategy of dietary chemoprevention

The Potential Role of Major Argan Oil Compounds as Nrf2 Regulators and Their Antioxidant Effects

In recent years, research on the discovery of natural compounds with potent antioxidant properties has resulted in growing interest in these compounds due to their potential therapeutic applications in oxidative-stress-related diseases. Argan oil, derived from the kernels of a native tree from Morocco, Argania spinosa, is renowned for its rich composition of bioactive compounds, prominently tocopherols, polyphenols, and fatty acids. Interestingly, a large body of data has shown that several components of argan oil activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, playing a crucial role in the cellular defense against oxidative stress. Activation of this Nrf2 pathway by argan oil components leads to the increased expression of downstream target proteins like NAD(P)H quinone oxidoreductase (NQO1), superoxide dismutase (SOD), heme oxygenase 1 (HO-1), and catalase (CAT). Such Nrf2 activation accounts for several health benefits related to antioxidant defense, anti-inflammatory effects, cardiovascular health, and neuroprotection in organisms. Furthermore, the synergistic action of the bioactive compounds in argan oil enhances the Nrf2 pathway. Accordingly, the modulation of the Kelch-like ECH associated protein 1 (Keap1)/Nrf2 signaling pathway by these components highlights the potential of argan oil in protecting cells from oxidative stress and underlines its relevance in dietetic prevention and therapeutic applications. This review aims to provide an overview of how major compounds in argan oil activate the Nrf2 pathway, updating our knowledge on their mechanisms of action and associated health benefits

Peroxisomal Acyl-CoA Oxidase Type 1: Anti-Inflammatory and Anti-Aging Properties with a Special Emphasis on Studies with LPS and Argan Oil as a Model Transposable to Aging

To clarify appropriateness of current claims for health and wellness virtues of argan oil, studies were conducted in inflammatory states. LPS induces inflammation with reduction of PGC1-α signaling and energy metabolism. Argan oil protected the liver against LPS toxicity and interestingly enough preservation of peroxisomal acyl-CoA oxidase type 1 (ACOX1) activity against depression by LPS. This model of LPS-driven toxicity circumvented by argan oil along with a key anti-inflammatory role attributed to ACOX1 has been here transposed to model aging. This view is consistent with known physiological role of ACOX1 in yielding precursors of specialized proresolving mediators (SPM) and with characteristics of aging and related disorders including reduced PGC1-α function and improvement by strategies rising ACOX1 (via hormonal gut FGF19 and nordihydroguaiaretic acid in metabolic syndrome and diabetes conditions) and SPM (neurodegenerative disorders, atherosclerosis, and stroke). Delay of aging to resolve inflammation results from altered production of SPM, SPM improving most aging disorders. The strategic metabolic place of ACOX1, upstream of SPM biosynthesis, along with ability of ACOX1 preservation/induction and SPM to improve aging-related disorders and known association of aging with drop in ACOX1 and SPM, all converge to conclude that ACOX1 represents a previously unsuspected and currently emerging antiaging protein