Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet.

We investigated the effects of eicosapentaenoic acid (EPA) on prevention (P) and reversal (R) of high saturated-fat (HF) diet-induced obesity and glucose-insulin homeostasis. Male C57BL/6J mice were fed low-fat (LF; 10% energy from fat), HF (45% energy from fat), or a HF-EPA-P (45% energy from fat; 36 g/kg EPA) diet for 11 wk. A 4th group was initially fed HF for 6 wk followed by the HF-EPA-R diet for 5 wk. As expected, mice fed the HF diet developed obesity and glucose intolerance. In contrast, mice fed the HF-EPA-P diet maintained normal glucose tolerance despite weight gain compared with the LF group. Whereas the HF group developed hyperglycemia and hyperinsulinemia, both HF-EPA groups (P and R) exhibited normal glycemia and insulinemia. Further, plasma adiponectin concentration was lower in the HF group but was comparable in the LF and HF-EPA groups, suggesting a role of EPA in preventing and improving insulin resistance induced by HF feeding. Further analysis of adipose tissue adipokine levels and proteomic studies in cultured adipocytes indicated that dietary EPA supplementation of HF diets was associated with reduced adipose inflammation and lipogenesis and elevated markers of fatty acid oxidation. In C57BL/6J mice, EPA minimized saturated fat-induced insulin resistance and this is in part mediated by its effects on fatty acid oxidation and inflammation.

/pdf/eicosapentaenoic-acid-prevents-and-reverses-insulin-2yop49941c.pdf

Eicosapentaenoic Acid Prevents and Reverses Insulin Resistance in High-Fat Diet-Induced Obese Mice via Modulation of Adipose Tissue Inflammation

Strategies to reduce obesity have become public health priorities as the prevalence of obesity has risen in the United States and around the world. While the anti-inflammatory and hypotriglyceridemic properties of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) are well known, their antiobesity effects and efficacy against metabolic syndrome, especially in humans, are still under debate. In animal models, evidence consistently suggests a role for n-3 PUFAs in reducing fat mass, particularly in the retroperitoneal and epididymal regions. In humans, however, published research suggests that though n-3 PUFAs may not aid weight loss, they may attenuate further weight gain and could be useful in the diet or as a supplement to help maintain weight loss. Proposed mechanisms by which n-3 PUFAs may work to improve body composition and counteract obesity-related metabolic changes include modulating lipid metabolism; regulating adipokines, such as adiponectin and leptin; alleviating adipose tissue inflammation; promoting adipogenesis and altering epigenetic mechanisms.

Omega-3 fatty acids in obesity and metabolic syndrome: a mechanistic update.

The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since then, researchers have conducted numerous in vitro and in vivo studies that consistently confirmed the antidiabetic activity of banaba. Scientists have identified different components of banaba to be responsible for its activity. Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound. More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds. The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity. In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chen et al. showed that the banaba water extract exhibited an insulin-like glucose transport inducing activity. Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid. Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin. A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin. Chen et al. have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes. The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG.

/pdf/antidiabetes-and-anti-obesity-activity-of-lagerstroemia-br4bvwvpgo.pdf

Antidiabetes and Anti-obesity Activity of Lagerstroemia speciosa.

Objectives The therapeutic benefits of argan oil consumption have been claimed by natives of Morocco and explorers for more than eight centuries. However, argan oil has remained unresearched for a long time. Traditionally, argan oil has been well known for its cardioprotective properties and it is also used in the treatment of skin infections. Argan oil is principally composed of mono-unsaturated (up to 80%) and saturated (up to 20%) fatty acids. As minor components, it contains polyphenols, tocopherols, sterols, squalene, and triterpene alcohols. Together with the mono-unsaturated fatty acids, these minor components are likely to be responsible for its beneficial effects. This review aims to present an overview of the known pharmacological properties of argan oil.

Key findings  Antiproliferative, antidiabetic, and cardiovascular-protective effects of argan oil have been particularly actively evaluated over the last 5 years in order to build on phytochemical studies that indicate the presence of large amounts of possibly pharmacologically active compounds.

Summary  This review shows that a lack of clinical data constitutes a serious weakness in our knowledge about argan oil, therefore it is difficult to correlate the reported pharmacological activities to any potential clinical relevance.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.2042-7158.2010.01190.x

Therapeutic potential of argan oil: a review

We investigated the potential metabolic benefits of fish oil (FO) or vegetable argan oil (AO) intake in a dietary model of obesity-linked insulin resistance. Rats were fed a standard chow diet (controls), a high-fat/high-sucrose (HFHS) diet, or an HFHS diet in which 6% of the fat was replaced by either FO or AO feeding, respectively. The HFHS diet increased adipose tissue weight and insulin resistance as revealed by increased fasting glucose and exaggerated glycemic and insulin responses to a glucose tolerance test (intraperitoneal glucose tolerance test). Fish oil feeding prevented fat accretion, reduced fasting glycemia, and normalized glycemic or insulin responses to intraperitoneal glucose tolerance test as compared with HFHS diet. Unlike FO consumption, AO intake failed to prevent obesity, yet restored fasting glycemia back to chow-fed control values. Insulin-induced phosphorylation of Akt and Erk in adipose tissues, skeletal muscles, and liver was greatly attenuated in HFHS rats as compared with chow-fed controls. High-fat/high-sucrose diet–induced insulin resistance was also confirmed in isolated hepatocytes. Fish oil intake prevented insulin resistance by improving or fully restoring insulin signaling responses in all tissues and isolated hepatocytes. Argan oil intake also improved insulin-dependent phosphorylations of Akt and Erk; and in adipose tissue, these responses were increased even beyond values observed in chow-fed controls. Taken together, these results strongly support the beneficial action of FO on diet-induced insulin resistance and glucose intolerance, an effect likely explained by the ability of FO to prevent HFHSinduced adiposity. Our data also show for the first time that AO can improve some of the metabolic and insulin signaling abnormalities associated with HFHS feeding.

Fish oil and argan oil intake differently modulate insulin resistance and glucose intolerance in a rat model of dietary-induced obesity.

Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [3H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

/pdf/insulin-sensitizing-and-anti-proliferative-effects-of-rc9kc2tk90.pdf

Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

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Fish oil and argan oil intake differently modulate insulin resistance and glucose intolerance in a rat model of dietary-induced obesity.

Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts