New Evidence on the Antiproliferative Activity of Campomanesia Adamantium (Cambess.) O. Berg Extracts in Melanoma Lung Metastasis.

Given the importance of discovering plant species from the Brazilian Cerrado biome with anticancer potential, this study evaluated the antitumor activity of two extracts of Campomanesi adamantium fruits in in vitro and in vivo models of melanoma lung metastasis. Pulp and peel extracts (DEGPU and DEGPE, respectively) were extracted from fresh fruit using dichloromethane as a solvent. As cytotoxicity parameter, concentration values that inhibited 50% cell growth (GI50), total growth inhibition (TGI), and selectivity index (SI) were established. The melanoma lung metastasis model was obtained by injecting 5 × 105/50 µL B16-F10 cells via the tail vein of mice, which received treatment on the 15th day. Metastatic lungs were collected for fluorescence analysis with the IR-780 marker and also macro- and microscopic assessment. In vitro analyses showed that DEGPU was active in K562 (GI50 32.99; TGI 47.93) and U-251 (GI50 32.10; TGI 249.92), whereas DEGPE showed better cytotoxicity results for all tumor cell lines, but was more efficient in K562 (GI50 27.42; TGI 40.20) and U-251 (GI50 4.89; TGI 12.77). Both showed a cytocidal effect on B16F10 at the highest concentration tested, with approximately 25% (DEGPU) and 88% (DEGPE) of cell death. In vivo analyzes showed that both extracts showed significant activity in metastatic lung. Fluorescence images showed differences in intensity between groups owing to greater tumor involvement. Macro- and microscopic images showed that treatments with extracts limited tumor growth and prevented proliferation. The extracts tested have promising activity, thus requiring further research on their active compounds.

Nutraceutical Potential of Grape (Vitis vinifera L.) Seed Oil in Oxidative Stress, Inflammation, Obesity and Metabolic Alterations.

Vitis vinifera L. (grapevine) is a perennial plant of the Vitaceae family that is widely used to produce grapes and wines. Grape seed oil is rich in fatty acids such as linoleic acid (65-75%), vitamin E (50 mg), and phytosterols in addition to phenolic compounds, such as catechins (414 mg), epicatechins (130.4 mg), and gallic acid (77 µg), shows promise as a nutritional compound and is outstanding as a therapeutic substance with active properties for health, detected mainly by in vitro studies, as well as some in vivo studies. The benefits of consuming this oil include modulating the expression of antioxidant enzymes, anti-atherosclerotic and anti-inflammatory effects, and protection against oxidative cell damage and some types of cancer. However, experimental findings confirm that therapeutic functions remain scarce; thus, more studies are needed to determine the mechanisms of action involved in the indicated therapeutic qualities.

Reply to Boucher, B.J. Comment on "Lopes et al. Adiposity Metabolic Consequences for Adolescent Bone Health. Nutrients 2022, 14, 3260".

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Investigating Effects of IR-780 in Animal Models of B16-F10 Melanoma: New Approach in Lung Metastasis.

IR-780 is a fluorescent marker, photostable and non-toxic, and is widely used in tumor targeting; however, studies on the impact of IR-780 in animal models of B16-F10 melanoma are scarce in the literature. Therefore, this study aims to analyze behavior of this marker in melanoma cells using in vitro and in vivo analyses with fluorescence microscopy to conduct an analysis of cell culture, and an in vivo imaging system for an analysis of cell culture, tumor targeting on animals, and organ examination. In vitro analysis showed that B16-F10 cells at a concentration of 2 × 105 cells.plate-1 allowed a better visualization using 20 µM of IR-780. Furthermore, the location of IR-780 accumulation was confirmed by its fluorescence microscopy. Through in vivo studies, fluorescence was not observed in subcutaneous nodules, and it was found that animals that received intraperitoneal injection of B16-F10 cells presented ascites and did not absorb IR-780. Additionally, animals exhibiting lung metastasis showed fluorescence in ex vivo lung images. Therefore, use of the IR-780 marker for evaluating the progression of tumor growth did not demonstrate efficiency; however, it was effective in diagnosing pulmonary metastatic tumors. Although this marker presented limitations, results of evaluating pulmonary involvement through ex vivo fluorescence imaging were determined based on intensity of fluorescence.

Effects of Ethanolic and Aqueous Extracts of Garcinia gardneriana Leaves in an In Vivo Experimental Model Induced by a Hyperlipidic Diet.

The study of medicinal plants, such as the genus Garcinia (Clusiaceae), in the treatment of non-communicable chronic diseases has aroused the interest of researchers. However, there are no studies in the literature that have investigated the effects of Garcinia gardneriana in experimental models of obesity for possible metabolic alterations. Swiss mice receiving a high-fat diet were supplemented with aqueous or ethanolic extract of G. gardneriana at doses of 200 or 400 mg/kg/day. It was found that there was a reduction in food consumption in experimental groups compared with the control groups, and the group supplemented with aqueous extract at a dose of 200 mg/kg/daydisplayed a reduction in weight. The results showed an increase in the values of high density lipoprotein (HDL-c), total cholesterol, triglycerides and fasting blood glucose. G. gardneriana did not protect against insulin resistance, and caused in an increase in monocyte chemoattractant protein-1 (MCP-1) concentrations and a reduction in interleukin 10 (IL-10). In addition, hepatic steatosis and microvesicular steatosis were indicated. It was revealed that, under the experimental conditions in the study, G. gardneriana did not prevent weight gain or comorbidities; that is, a different behavior was obtained from that described in the literature with regard to the medicinal potential of the Garcinia species, which is probably related to the phytochemical properties.

Data on fatty acid profile, optical properties and oxidative stability of sunflower oils used in the treatment of skin wounds.

This dataset describes the analysis of aflatoxins, macroelement and microelement concentration, oxidative stability and fatty acid profile of infant formula milk powder. Gas chromatography (CG) was used to identity 14 fatty acid methyl esters in in five samples of oils. The Racimat 893 method (induction times), Thermogravimetry (TG), Derivative Thermogravimetry (DTG) and Differential Scanning Calorimetry (DSC) were used to estimate the oxidative stability of oils. In addition, UV-VIS spectroscopic techniques were employed to obtain graphs of the absorption of each oil. The data presented can be useful in identifying compounds available in oils used to promote wound healing and understand the degradation mechanism.

Effect of Fiber Supplementation on Systemic Inflammation and Liver Steatosis in Mice Fed with High-Carbohydrate Diets.

Background: High consumption of carbohydrates can trigger metabolic and inflammatory disorders in the body. Thus, the aim of this study was to evaluate the effect of fiber supplementation on inflammation and hepatic steatosis in mice fed high-carbohydrate diets. Methods: Swiss male mice were distributed into two control groups and two experimental groups that received isocaloric diet rich in starch (55%) or rich in fructose (55%). In the last 4 weeks of the experiment, the animals received 5% fructo-oligosaccharide (FOS) supplementation via gavage, or water in the control groups. After 16 weeks, biochemical analyses, inflammatory cytokines, and histology of the liver of the animals were performed. Results: The animals that received fructose had higher weight at the end of the experiment as well as liver weight, consumed more feed, had higher levels of tumor necrosis factor (TNF) and monocyte chemoattractant protein-1 (MCP-1), and a higher degree of hepatic steatosis when compared with the animals that received starch. However, the animals that received starch showed a higher inflammatory process. FOS supplementation was efficient in reducing liver weight and hepatic steatosis degree in animals fed with fructose diet but showed more degeneration of liver tissue and high levels of inflammatory cytokines. FOS reduced the levels of urea and total cholesterol in the starch-fed animals. Conclusions: Diets rich in carbohydrates such as starch and fructose cause deleterious effects in animals, and fiber supplementation can bring beneficial effects.

Oxidative stability and elemental analysis of sunflower (Helianthus annuus) edible oil produced in Brazil using a domestic extraction machine.

The consumption of regular vegetable oils has been linked to energy acquisition, nutritional benefits, health improvement, and the regulation of metabolic diseases. This study evaluated fatty acids composition, physicochemical, thermal, oxidative, and optical properties, and quantified trace elements in the sunflower oil extracted by a domestic cold-press machine. The oil presented linoleic (54.00%) and oleic (37.29%) primary unsaturated fatty acids (91.67%), in which atherogenic (0.05), thrombogenic (0.16), hypocholesterolemic/hypercholesterolemic (21.97), peroxide (16.16), saponification (141.80), and relative density indices (0.92) demonstrated to be suitable for human consumption and possible health promotion. In addition, the concentrations of trace elements by ICP OES were ordered Zn > Fe > Al > Cu > Mn > Cr. Concentrations of Zn, Fe, Al, Cu, and Mn were lower than FAO/WHO and DRI/AI limits, while Cr concentrations exceeded the FAO/WHO limits, which can be used as an indicator of the polluted ambiance. Sunflower oil quantities daily consumption were calculated by taking into account non-carcinogenic risk (CR < 10-4), and total non-carcinogenic hazard index (HI < 1). Based on trace elements determined in this study, the suitable quantity of sunflower oil consumption varies according to individuals aged 8, 18, and 30 years and will be deemed 0.61, 1.46, and 1.65 g/kg, respectively, attending HI = 0.99 and CR < 10-4.

Adiposity Metabolic Consequences for Adolescent Bone Health.

Infancy and adolescence are crucial periods for bone health, since they are characterized by intense physical growth and bone development. The unsatisfactory acquisition of bone mass in this phase has consequences in adult life and increases the risk of developing bone diseases at more advanced ages. Nutrient deficiencies, especially calcium and vitamin D, associated with a sedentary lifestyle; lack of sun exposure; and epigenetic aspects represent some of the main risk factors for poor bone quality. In addition, recent studies relate childhood obesity to impaired bone health; however, studies on the adiposity effects on bone health are scarce and inconclusive. Another gap concerns the implications of obesity on child sexual maturity, which can jeopardize their genetic potential bone mass and increase fracture risk. Therefore, we reviewed the analyzed factors related to bone health and their association with obesity and metabolic syndrome in adolescents. We concluded that obesity (specifically, accumulated visceral fat) harms bones in the infant-juvenile phase, thereby increasing osteopenia/osteoporosis in adults and the elderly. Thus, it becomes evident that forming and maintaining healthy eating habits is necessary during infancy and adolescence to reduce the risk of fractures caused by bone-metabolic diseases in adulthood and to promote healthy ageing.

Natural Antioxidant Evaluation: A Review of Detection Methods.

Antioxidants have drawn the attention of the scientific community due to being related to the prevention of various degenerative diseases. The antioxidant capacity has been extensively studied in vitro, and different methods have been used to assess its activity. However, the main issues related to studying natural antioxidants are evaluating whether these antioxidants demonstrate a key role in the biological system and assessing their bioavailability in the organism. The majority of outcomes in the literature are controversial due to a lack of method standardization and their proper application. Therefore, this study aims to compile the main issues concerning the natural antioxidant field of study, comparing the most common in vitro methods to evaluate the antioxidant activity of natural compounds, demonstrating the antioxidant activity in biological systems and the role of the main antioxidant enzymes of redox cellular signaling and explaining how the bioavailability of bioactive compounds is evaluated in animal models and human clinical trials.

Omega-3 Fatty Acids and Balanced Gut Microbiota on Chronic Inflammatory Diseases: A Close Look at Ulcerative Colitis and Rheumatoid Arthritis Pathogenesis.

The aim of this article was to review experimental and clinical studies regarding the use of omega-3 fatty acids on the prevention and control of chronic inflammatory diseases with autoimmune background through the gut microbiota modulation. For this, natural omega-3 sources are presented emphasizing the importance of a healthy diet for the body's homeostasis and the enzymatic processes that these fatty acids go through once inside the body. The pathogenesis of ulcerative colitis and rheumatoid arthritis are revisited under the light of the gut microbiota dysbiosis approach and how those fatty acids are able to prevent and control these two pathological conditions that are responsible for the global chronic burden and functional disability and life-threatening comorbidities if not treated properly. As a matter of reflection, as we are living a pandemic crisis owing to COVID-19 infection, we present the potential of omega-3 in preventing a poor prognosis once they contribute to balancing the immune system modulation the inflammatory process.

Linseed, Baru, and Coconut Oils: NMR-Based Metabolomics, Leukocyte Infiltration Potential In Vivo, and Their Oil Characterization. Are There Still Controversies?

Different fatty acid proportions produce potential inflammatory and metabolic changes in organisms. However, the evidence for how each fatty acid mediates the metabolic pathway, and its lipid stability remains controversial. To resolve this controversy, the present study investigated the metabolic effects of cold-pressed linseed (LG), coconut (CG), and baru (BG) oils in comparison to those of soybean oil (SG) in mice, in terms of their oil characterization and stability. The quality analysis showed less oxidative behavior among PUFA-rich oils (SO, BO, and LO, with induction periods lower than 2 h compared to 39.8 h for CG), besides the high contents of tocopherols and carotenoids in SG and LG. In the experimental study, CG presented higher triglyceride (257.93 ± 72.30) and VLDL-cholesterol levels (51.59 ± 14.46, p < 0.05), while LG reduced LDL levels (59.29 ± 7.56, p < 0.05) when compared to SG (183.14 ± 22.06, 36.63 ± 4.41 and 131.63 ± 29.0, respectively). For visceral fats, the adiposity index was lower for BG (7.32 ± 3.13) and CG (9.58 ± 1.02, p < 0.05) in relation to SG (12.53 ± 2.80), and for leukocyte recruitment, CG presented lower polymorphonuclear (PMN) (p < 0.0001) and mononuclear (MN) (p < 0.05) cell infiltration, demonstrating anti-inflammatory potential. In NMR-based metabolomics, although CG presented higher values for the glucose, lactate, and LDL/VLDL ratio, this group also evidenced high levels of choline, a lipotropic metabolite. Our study emphasized the controversies of saturated fatty acids, which impair serum lipids, while alfa-linolenic acid presented cardioprotective effects. However, coconut oil also has a positive immunomodulatory pathway and was found to reduce visceral bodyfat in mice. Therefore, for future applications, we suggest a combination of lauric and al-fa-linolenic acid sources, which are present in coconut and linseed oil, respectively. This combination could be less obesogenic and inflammatory and exert cardioprotective action.

Relationship between intestinal microbiota, diet and biological systems: an integrated view.

The health-disease process can be influenced by the intestinal microbiota. As this plays a fundamental role in protecting the organism, the importance of studying the composition and diversity of this community becomes increasingly evident. Changes in the composition of the intestinal bacterial community may result in dysbiosis, and this process may contribute to triggering various diseases in all biological systems. This imbalance of intestinal microbiota homeostasis may alter commensal bacteria and the host metabolism, as well as immune function. Dysbiosis also causes an increase in intestinal permeability due to exposure to molecular patterns associated with the pathogen and lipopolysaccharides, leading to a chronic inflammatory process that can result in diseases for all biological systems. In this context, dietary intervention through the use of probiotics, prebiotics and antioxidant foods can be considered a contribution to the modulation of intestinal microbiota. Probiotics have been used to provide up to 10 billion colony forming units, and probiotic foods, Kefir and fermented natural yogurt are also used. Prebiotics, in turn, are found in supplemental formulations of processed foods and in functional foods that are also sources of phenolic compounds, such as flavonoids, antioxidant and anti-inflammatory substances, polyunsaturated fatty acids, vitamins, and minerals. In this review, we will discuss the relationship between an imbalance in the intestinal microbiota with the development of diseases, besides indicating the need for future studies that can establish bacterial parameters for the gastrointestinal tract by modulating the intestinal microbiota, associated with the adoption of healthy habits during all life cycles.

High-Fat Diet with Lyophilized Acrocomia aculeata Pulp Increases High-Density Lipoprotein-Cholesterol Levels and Inhibits Adipocyte Hypertrophy in Mice.

Obesity is a relevant health hazard characterized as a chronic noncommunicable disease, with severe comorbidities that cause mortality worldwide. Acrocomia aculeata is a Brazilian palm with edible fruits. Its pulp contains fibers, monounsaturated fatty acids (MUFAs), such as oleic acid and carotenoids. In this context, our study aimed to elucidate the protective effect of the lyophilized A. aculeata pulp added at the rates of 1%, 2%, and 4% to a high-fat (HF) diet (rich in saturated fats and cholesterol), for 90 days, in mice. The treatment with 4% pulp induced a significant increase in the biochemical parameters of serum cholesterol HDL-C (high-density lipoprotein) compared with the control. According to the evaluation of the epididymal tissue, the groups treated with A. aculeata pulp exhibited smaller fat deposits compared with the HF diet group. Therefore, we infer that the predominant components in A. aculeata, particularly fibers and MUFAs, promote beneficial effects on health parameters during simultaneous exposure to food rich in saturated fat and cholesterol, typical of the Western diet. This is the first study to correlate the presence of fatty acids from A. aculeata pulp in different proportions added in a HF diet with metabolic and histological parameters in Swiss mice.

Do Bioactive Food Compound with Avena sativa L., Linum usitatissimum L. and Glycine max L. Supplementation with Moringa oleifera Lam. Have a Role against Nutritional Disorders? An Overview of the In Vitro and In Vivo Evidence.

Functional clinical nutrition is an integrative science; it uses dietary strategies, functional foods and medicinal plants, as well as combinations thereof. Both functional foods and medicinal plants, whether associated or not, form nutraceuticals, which can bring benefits to health, in addition to being included in the prevention and treatment of diseases. Some functional food effects from Avena sativa L. (oats), Linum usitatissimum L. (brown flaxseed), Glycine max L. (soya) and Moringa oleifera have been proposed for nutritional disorders through in vitro and in vivo tests. A formulation called a bioactive food compound (BFC) showed efficiency in the association of oats, flaxseed and soy for dyslipidemia and obesity. In this review, we discuss the effects of BFC in other nutritional disorders, as well as the beneficial effects of M. oleifera in obesity, cardiovascular disease, diabetes mellitus type 2, metabolic syndrome, intestinal inflammatory diseases/colorectal carcinogenesis and malnutrition. In addition, we hypothesized that a BFC enriched with M. oleifera could present a synergistic effect and play a potential benefit in nutritional disorders. The traditional consumption of M. oleifera preparations can allow associations with other formulations, such as BFC. These nutraceutical formulations can be easily accepted and can be used in sweet preparations (fruit and/or vegetable juices, fruit and/or vegetable vitamins, porridges, yogurt, cream, mousses or fruit salads, cakes and cookies) or savory (vegetable purees, soups, broths and various sauces), cooked or not. These formulations can be low-cost and easy-to-use. The association of bioactive food substances in dietary formulations can facilitate adherence to consumption and, thus, contribute to the planning of future nutritional interventions for the prevention and adjuvant treatment of the clinical conditions presented in this study. This can be extended to the general population. However, an investigation through clinical studies is needed to prove applicability in humans.

High Concentration of Heavy Metal and Metalloid Levels in Edible Campomanesia adamantium Pulp from Anthropic Areas.

This study aimed to quantify the extent of heavy metal, non-metal and metalloid levels in the Campomanesia adamantium pulp obtained from an area crossed by road experiencing high large vehicle traffic and intensive agriculture modern farming, to monitor the health risks associated with pulp consumption by humans. For this purpose, in three spots located within this area, ripe fruits were collected on the roadside, bush and farm-margin. Pulp samples were digested by microwave-assisted equipment, and chemical elements were quantified by ICP OES. The concentrations of K, Pb, Se, Fe, Mo, Zn, Co, Ni and Mn in the pulp collected in roadside/bush points showed statistical differences (p < 0.05). The heavy metals and metalloid concentrations that exceeded FAO/WHO standards were ordered Pb > As > Mo > Co > Ni > Mn > Cr. Therefore, among these metalloid and heavy metals, As, Pb and Cr were found to be higher in farm-margin > roadside > bush (1.5 × 10-3, 1.1 × 10-3 and 6.2 × 10-4), respectively. Therefore, As is the most important metalloid with higher levels in farm-margin, roadside and bush (1.5 × 10-3, 1.0 × 10-3 and 6.0 × 10-4 > 10-6-10-4 and 3.33, 2.30 and 1.34 > 1), respectively, to total cancer risk and hazard quotient, if 10 g daily of pulp are consumed.

Polyphenols and ω-3 PUFAs: Beneficial Outcomes to Obesity and Its Related Metabolic Diseases.

Obesity is associated with the leading causes of death in the worldwide. On the other hand, the intake of vegetables, fruits and fish is related to the reduction of obesity and other metabolic syndromes. This review aims to highlight the role of ingestion of polyphenols and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in reducing obesity and related metabolic diseases (RMDs). The consumption of vegetables, fish and by-products rich in polyphenols and α-linolenic acid (ALA), as well as oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with a decrease in obesity and its RMDs in consumers. Furthermore, we discussed the adequate amount of extracts, powder, polyphenols, ω-3 PUFAs administrated in animal models and human subjects, and the relevant outcomes obtained. Thus, we appeal to the research institutions and departments of the Ministries of Health in each country to develop a food education joint project to help schools, businesses and families with the aim of reducing obesity and other metabolic diseases.

ß-Carotene: Preventive Role for Type 2 Diabetes Mellitus and Obesity: A Review.

Carotenoids are vital antioxidants for plants and animals. They protect cells from oxidative events and act against the inflammatory process and carcinogenesis. Among the most abundant carotenoids in human and foods is ß-carotene. This carotenoid has the highest level of provitamin A activity, as it splits into two molecules of retinol through the actions of the cytosolic enzymes: ß-carotene-15,15'-monooxygenase (ß-carotene-15,15'-oxygenase 1) and ß-carotene-9',10'-dioxygenase (ß-carotene-9',10'-oxygenase 2). The literature supports the idea that ß-carotene acts against type 2 diabetes mellitus, cardiovascular diseases, obesity, and metabolic syndrome. Due to the many processes involved in ß-carotene biosynthesis and metabolic function, little is known about such components, since many mechanisms have not yet been fully elucidated. Therefore, our study concisely described the relationships between the consumption of carotenoids, with emphasis on ß-carotene, and obesity and type 2 diabetes mellitus and its associated parameters in order to understand the preventive role of carotenoids better and encourage their consumption.

Minerals in Pregnancy and Their Impact on Child Growth and Development.

During pregnancy, women undergo metabolic and physiological changes, and their needs are higher, to maintain growth and development of the fetus. If the nutritional status of the expectant mother is not satisfactory, some maternal and neonatal complications can occur. In the second and third trimester of pregnancy, there is a reserve of nutrients in the fetus that can be utilized after birth; thereby, children present an accelerated growth in the first years of life, which is a proven response to the available nutrition pattern. However, if such a pattern is insufficient, there will be deficits during development, including brain function. Therefore, despite many recent published works about gestational nutrition, uncertainties still remain on the mechanisms of absorption, distribution, and excretion of micronutrients. Further elucidation is needed to better understand the impacts caused either by deficiency or excess of some micronutrients. Thus, to illustrate the contributions of minerals during prenatal development and in children, iodine, selenium, iron, zinc, calcium, and magnesium were selected. Our study sought to review the consequences related to gestational deficiency of the referred minerals and their impact on growth and development in children born from mothers with such deficiencies.

Therapeutic Effects of Morinda citrifolia Linn. (Noni) Aqueous Fruit Extract on the Glucose and Lipid Metabolism in High-Fat/High-Fructose-Fed Swiss Mice.

The aim of this study was to evaluate the therapeutic effects of two different doses (250 and 500 mg/kg) of Morinda citrifolia fruit aqueous extract (AE) in high-fat/high-fructose-fed Swiss mice. The food intake, body weight, serum biochemical, oral glucose tolerance test (OGTT), and enzyme-linked immunosorbent assay (ELISA), as well as histological analyses of the liver, pancreatic, and epididymal adipose tissue, were used to determine the biochemical and histological parameters. The chemical profile of the extract was determined by ultra-fast liquid chromatography-diode array detector-tandem mass spectrometry (UFLC-DAD-MS), and quantitative real-time PCR (qRT-PCR) was used to evaluate the gene expressions involved in the lipid and glucose metabolism, such as peroxisome proliferative-activated receptors-γ (PPAR-γ), -α (PPAR-α), fatty acid synthase (FAS), glucose-6-phosphatase (G6P), sterol regulatory binding protein-1c (SREBP-1c), carbohydrate-responsive element-binding protein (ChREBP), and fetuin-A. Seventeen compounds were tentatively identified, including iridoids, noniosides, and the flavonoid rutin. The higher dose of AE (AE 500 mg/kg) was demonstrated to improve the glucose tolerance; however, both doses did not have effects on the other metabolic and histological parameters. AE at 500 mg/kg downregulated the PPAR-γ, SREBP-1c, and fetuin-A mRNA in the liver and upregulated the PPAR-α mRNA in white adipose tissue, suggesting that the hypoglycemic effects could be associated with the expression of genes involved in de novo lipogenesis.