The dietary protein/carbohydrate ratio differentially modifies lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation.

During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis

The expression of metabolic genes in the liver of dams fed different proportions (10/73, 20/63 or 30/53%) of dietary protein/dietary carbohydrates (DP/DCH) during gestation and lactation.

<p>(A) The relative mRNA levels of sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FAS), and pyruvate kinase (PK). (B) A representative immunoblot of AMP-activated protein kinase (AMPK), threonine phosphorylation of AMP-activated protein kinase (P-AMPK), p70 S6 kinase (S6K), threonine phosphorylation of S6 kinase (P-S6K), fatty acid synthase (FAS) and actin. (C) Western blot densitometric analysis of FAS/ACTIN. (D) A representative histology picture of the liver of rats fed 10/73, 20/63 or 30/53% DP/DCH at day 5 of lactation. Western blot densitometric analysis of (E) P-S6K/S6K, (F) P-AMPK/AMPK. (G) The relative mRNA levels of serine dehydratase (SDH). Values are the mean ± SEM of three different blots. n = 5. **p<0.01, ***p<0.001.</p

Composition of the experimental diets used in this study.

a<p>Teklad test diets.</p>b<p>Rogers-Harper, Teklad test diets.</p>c<p>Vitamin mix, Teklad 40060 (milligrams per kilogram diet): p-aminobenzoic acid, 110; ascorbic acid, 991; biotin, 0.4; vitamin B12, 30; calcium pantothenate, 66; choline dihydrogen citrate, 3497; folic acid, 2; inositol, 110; menadione, 50; niacin, 99; pyridoxine HCl, 22; riboflavin, 22; thiamin HCl, 22; vitamin A palmitate, 40; cholecalciferol, 4; and vitamin.</p

The expression of genes involved in lipid oxidation and lipolysis in the mammary gland of dams fed different proportions (10/73, 20/63 or 30/53%) of dietary protein/dietary carbohydrates (DP/DCH) during gestation and lactation.

<p>(A) The relative mRNA levels of carnitine palmitoyl transferase 1 (CPT-1) and (B) hormone sensitive lipase (HSL). Values are the mean ± SEM. n = 5. *p<0.05, **p<0.01, ***p<0.001.</p

Food intake, body weight of dams fed different proportions (10/73, 20/63 or 30/53%) of dietary protein/dietary carbohydrate (DP/DCH) during gestation and lactation, as well as the pups’ weight gain.

<p>(A) The food intake, (B) weight gain of dams and (C) weight gain of pups from dams fed different proportions of DP/DCH (10/73, 20/63 or 30/53%) during gestation and lactation. The Values are mean ± SEM. n = 5. **p<0.01,***p<0.001.</p

The expression of metabolic genes in the adipose tissue of dams fed different proportions (10/73, 20/63 or 30/53%) of dietary protein/dietary carbohydrates (DP/DCH) during gestation and lactation.

<p>(A) The relative mRNA levels of sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FAS), and hormone sensitive lipase (HSL). (B) A representative immunoblot of AMP-activated protein kinase (AMPK), threonine phosphorylation of AMP-activated protein kinase (P-AMPK), p70 S6 kinase (S6K), threonine phosphorylation of S6 kinase (P-S6K), fatty acid synthase (FAS) and actin. Western blot densitometric analysis of (C) FAS/ACTIN, (D) P-S6K/S6K and (E) P-AMPK/AMPK. Values are the mean ± SEM of three different blots. n = 5. *p<0.05, **p<0.01 ***p<0.001.</p

The genes and proteins involved in lipogenesis in the mammary gland of dams fed different proportions (10/73, 20/63 or 30/53%) of dietary protein/dietary carbohydrate (DP/DCH) during gestation and lactation.

<p>(A) The relative mRNA levels of sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FAS), and phosphoenolpyruvate carboxykinase (PEPCK). (B) Representative immunoblot of FAS and actin. (C) Western blot densitometric analysis of FAS/ACTIN. Values are the mean ± SEM of three different blots. n = 5. *p<0.05, ***p<0.001.</p

Occurrence and Potential Sources of Quinones Associated with PM2.5 in Guadalajara, Mexico

This study aims to establish the influence of primary emission sources and atmospheric transformation process contributing to the concentrations of quinones associated to particulate matter of less than 2.5 µm (PM2.5) in three sites within the Metropolitan Area of Guadalajara (MAG), namely Centro (CEN), Tlaquepaque (TLA) and Las Águilas (AGU). Environmental levels of quinones extracted from PM2.5 filters were analyzed using Gas Chromatography coupled to Mass Spectrometry (GC-MS). Overall, primary emissions in combination with photochemical and oxidation reactions contribute to the presence of quinones in the urban atmosphere of MAG. It was found that quinones in PM2.5 result from the contributions from direct emission sources by incomplete combustion of fossil fuels such as diesel and gasoline that relate mainly to vehicular activity intensity in the three sampling sites selected. However, this also suggests that the occurrence of quinones in MAG can be related to photochemical transformation of the parent Polycyclic Aromatic Hydrocarbons (PAHs), to chemical reactions with oxygenated species, or a combination of both routes. The higher concentration of 1,4-Chrysenequinone during the rainy season compared to the warm-dry season indicates chemical oxidation of chrysene, since the humidity could favor singlet oxygen collision with parent PAH present in the particle phase. On the contrary, 9,10-Anthraquinone/Anthracene and 1,4-Naftoquinone/Naphthalene ratios were higher during the warm-dry season compared to the rainy season, which might indicate a prevalence of the photochemical formation during the warm-dry season favored by the large solar radiation typical of the season. In addition, the estimated percentage of photochemical formation of 9,10-Phenanthrenequinone showed that the occurrence of this compound in Tlaquepaque (TLA) and Las Águilas (AGU) sites is mainly propagated by conditions of high solar radiation such as in the warm-dry season and during long periods of advection of air masses from emission to the reception areas. This was shown by the direct association between the number hourly back trajectories arriving in the TLA and AGU from Centro and other areas in MAG and the highest photochemical formation percentage

Ramon Flour (<i>Brosimum alicastrum</i> Swartz) Ameliorates Hepatic Lipid Accumulation, Induction of AMPK Phosphorylation, and Expression of the Hepatic Antioxidant System in a High-Fat-Diet-Induced Obesity Mouse Model

Excessive consumption of fat and carbohydrates, together with a decrease in traditional food intake, has been related to obesity and the development of metabolic alterations. Ramon seed is a traditional Mayan food used to obtain Ramon flour (RF) with high biological value in terms of protein, fiber, micronutrients, and bioactive compounds such as polyphenols. However, few studies have evaluated the beneficial effects of RF. Thus, we aimed to determine the metabolic effects of RF consumption on a high-fat-diet-induced obesity mouse model. We divided male BALB/c mice into four groups (n = 5 each group) and fed them for 90 days with the following diets: Control (C): control diet (AIN-93), C + RF: control diet adjusted with 25% RF, HFD: high-fat diet + 5% sugar in water, and HFD + RF: high-fat diet adjusted with 25% RF + 5% sugar in water. The RF prevented the increase in serum total cholesterol (TC) and alanine transaminase (ALT) that occurred in the C and HFD groups. Notably, RF together with HFD increased serum polyphenols and antioxidant activity, and it promoted a decrease in the adipocyte size in white adipose tissue, along with lower hepatic lipid accumulation than in the HFD group. In the liver, the HFD + RF group showed an increase in the expression of β-oxidation-related genes, and downregulation of the fatty acid synthase (Fas) gene compared with the HFD group. Moreover, the HFD + RF group had increased hepatic phosphorylation of AMP-activated protein kinase (AMPK), along with increased nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 2 (SOD2) protein expression compared with the HFD group. Thus, RF may be used as a nutritional strategy to decrease metabolic alterations during obesity

Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects

ObjectiveObesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity.Research design and methods45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of ≥30 and≤40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, the same variables were assessed including a serum metabolomic analysis, gut microbiota, and a skeletal muscle biopsy was obtained to study the gene expression of fatty acid oxidation.ResultsIn the present study, we show that the consumption of genistein for 2 months reduced insulin resistance in subjects with obesity, accompanied by a modification of the gut microbiota taxonomy, particularly by an increase in the Verrucomicrobia phylum. In addition, subjects showed a reduction in metabolic endotoxemia and an increase in 5′-adenosine monophosphate-activated protein kinase phosphorylation and expression of genes involved in fatty acid oxidation in skeletal muscle. As a result, there was an increase in circulating metabolites of β-oxidation and ω-oxidation, acyl-carnitines and ketone bodies.ConclusionsChange in the gut microbiota was accompanied by an improvement in insulin resistance and an increase in skeletal muscle fatty acid oxidation. Therefore, genistein could be used as a part of dietary strategies to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed