Genistein Stimulation of White Adipose Tissue Thermogenesis Is Partially Dependent on GPR30 in Mice.

SCOPE: Genistein increases whole body energy expenditure by stimulating white adipose tissue (WAT) browning and thermogenesis. G-Coupled receptor GPR30 can mediate some actions of genistein, however, it is not known whether it is involved in the activation of WAT-thermogenesis. Thus, the aim of the study is to determine whether genistein activates thermogenesis coupled to an increase in WAT browning and mitochondrial activity, in GPR30+/+ and GPR30-/- mice. METHODS AND RESULTS: GPR30+/+ and GPR30-/- mice are fed control or high fat sucrose diets containing or not genistein for 8 weeks. Body weight and composition, energy expenditure, glucose tolerance, and browning markers in WAT, and oxygen consumption rate, 3', 5'-cyclic adenosine monophosphate (cAMP) concentration and browning markers in adipocytes are evaluated. Genistein consumption reduces body weight and fat mass gain in a different extent in both genotypes, however, energy expenditure is lower in GPR30-/- compared to GPR30+/+ mice, accompanied by a reduction in browning markers, maximal mitochondrial respiration, cAMP concentration, and browning markers in cultured adipocytes from GPR30-/- mice. Genistein improves glucose tolerance in GPR30+/+ , but this is partially observed in GPR30-/- mice. CONCLUSION: The results show that GPR30 partially mediates genistein stimulation of WAT thermogenesis and the improvement of glucose tolerance.

Interaction between the amount of dietary protein and the environmental temperature on the expression of browning markers in adipose tissue of rats.

BACKGROUND: A low-protein diet increases the expression and circulating concentration of FGF21. FGF21 stimulates the browning process of WAT by enhancing the expression of UCP1 coupled with an increase in PGC1α. Interestingly, the consumption of a low-protein diet could stimulate WAT differentiation into beige/brite cells by increasing FGF21 expression and Ucp1 mRNA abundance. However, whether the stimulus of a low-protein diet on WAT browning can synergistically interact with another browning stimulus, such as cold exposure, remains elusive. RESULTS: In the present study, rats were fed 6% (low), 20% (adequate), or 50% (high) dietary protein for 10 days and subsequently exposed to 4 °C for 72 h. Body weight, food intake, and energy expenditure were measured, as well as WAT browning and BAT thermogenesis markers and FGF21 circulating levels. The results showed that during cold exposure, the consumption of a high-protein diet reduced UCP1, TBX1, Cidea, Cd137, and Prdm16 in WAT when compared with the consumption of a low-protein diet. In contrast, at room temperature, a low-protein diet increased the expression of UCP1, Cidea, and Prdm16 associated with an increase in FGF21 expression and circulating levels when compared with a consumption of a high-protein diet. Consequently, the consumption of a low-protein diet increased energy expenditure. CONCLUSIONS: These results indicate that in addition to the environmental temperature, WAT browning is nutritionally modulated by dietary protein, affecting whole-body energy expenditure.

Aguamiel concentrate from Agave salmiana and its extracted saponins attenuated obesity and hepatic steatosis and increased Akkermansia muciniphila in C57BL6 mice.

Obesity and its comorbidities are a severe public health problem worldwide. The use of bioactive compounds found in some foods has been demonstrated to ameliorate the metabolic abnormalities associated with obesity. The purpose of this study was to assess whether the bioactive compounds present in aguamiel concentrate (AC) from Agave salmiana could attenuate glucose intolerance and hepatic steatosis in mice fed a high fat (HF) diet. HPLC-ELSD analysis showed that AC contained several saponins. The consumption of an AC extract rich in saponins reduced weight gain and fat mass and lowered serum glucose, insulin and LDL-cholesterol levels in mice fed a HF diet. Additionally, mice fed the saponin extract exhibited a reduced HOMA index and hepatic lipid levels and increased expression of genes involved in fatty acid oxidation. Saponins increased white adipose tissue browning, AMPK phosphorylation, fatty acid oxidation, and mitochondrial activity in skeletal muscle and energy expenditure in mice fed the HF diet. These metabolic changes were accompanied by an increase in the abundance of Akkermansia muciniphila in the gut microbiota. Therefore, Agave salmiana saponins can be an alternative to attenuate the metabolic changes that accompany obesity.

The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a mouse model of diet induced obesity.

A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity.

Dietary type and amount of fat modulate lipid metabolism gene expression in liver and in adipose tissue in high-fat diet-fed rats.

BACKGROUND AND AIMS: Dietary fat plays a central role in the development of obesity. However, the metabolic consequences of dietary fat can vary depending on their fatty acid composition. Therefore, the aim of the present work was to study the effect of the type and amount of dietary fat on the expression of genes controlling lipogenesis and fatty acid oxidation in the liver or adipose tissue of rats. METHODS: The expression of hepatic or adipose tissue lipid metabolic genes from Sprague Dawley or Zucker(fa/fa) rats, respectively, was measured after chronic consumption of diets containing different types/amounts of dietary fats or after rats were adapted for 2 months to a high-fat Western diet and then fed different types and amounts of fats. RESULTS: Each fat or oil in the diet regulated differentially the expression of transcription factors involved in lipogenesis and fatty acid oxidation as well as some of its target genes in liver. The expression of these genes after a chronic consumption of a high-fat Western diet was reestablished in the presence of less dietary fat and was dependent on the type of fat. In obese Zucker(fa/fa) rats, consumption of a high-fat diet repressed the expression of lipogenic, fatty acid oxidation and thermogenic genes in adipose tissue. CONCLUSIONS: Type of fat influences the expression of genes that are involved in lipid metabolism in liver and adipose tissue, but this response is repressed when the amount of dietary fat is excessive, diminishing the differences between each type of fat.

Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat.

Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.

Changes in messenger RNA abundance of amino acid transporters in rat mammary gland during pregnancy, lactation, and weaning.

During lactation, the mammary gland increases the needs for nutrients to fulfill the milk production requirements. Among these nutrients, amino acids play an important role for the synthesis of milk proteins. Amino acids are supplied to the mammary gland through amino acid transporters, although some are synthesized in situ. The purpose of this study was to establish the pattern of changes in messenger RNA abundance of the amino acid transporters ASC, system L, EAAC1, GLAST, CAT-1, and Tau in the mammary gland of the rat during different stages of pregnancy and lactation. Rats were fed during pregnancy and lactation a 20% casein diet. Food intake increased significantly during the lactation period. Amino acid transporter ASC expression increased during the first days of pregnancy about 2-fold, and it was increased in a lesser extent again during the peak of lactation. The expression of system L (LAT-1) and CAT-1 transporters was increased only during the lactation period. On the other hand, the expression of the transporters for anionic amino acids EAAC1 and GLAST was low during both stages. Finally, taurine transporter expression decreased during pregnancy; and it was significantly lower during lactation. These results showed that amino acid transporters were not expressed similarly in the mammary gland during pregnancy and lactation, indicating that the expression of these transporters did not respond only to the metabolic needs of the gland but depended on the dietary protein supply and possibly the specific hormonal changes that occur during pregnancy and lactation.