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1.
Am J Clin Nutr ; 111(6): 1178-1189, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412597

RESUMO

BACKGROUND: There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined. OBJECTIVES: We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30-70 y at above-average risk of cardiovascular disease (CVD). METHODS: The study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point. RESULTS: Almonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference -0.25 mmol/L; 95% CI: -0.45, -0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation. CONCLUSIONS: Whole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD.This trial was registered at clinicaltrials.gov as NCT02907684.


Assuntos
Doenças Cardiovasculares/metabolismo , LDL-Colesterol/sangue , Endotélio Vascular/fisiopatologia , Gorduras/metabolismo , Fígado/metabolismo , Prunus dulcis/metabolismo , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nozes/metabolismo , Fatores de Risco , Lanches , Triglicerídeos/sangue , Vasodilatação
2.
J Sports Med Phys Fitness ; 60(4): 618-624, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32396288

RESUMO

BACKGROUND: The purpose of this study was to compare the effects of a 24-week resistance-training (RT) program performed 2 vs. 3 times per week on body fat and metabolic health markers in older women. METHODS: Thirty-nine women (≥60 years old) were randomly assigned to two groups according to RT frequency (G2x=two sessions per week, N.=19; and G3x=three sessions per week, N.=20) and were submitted to two 12-week stages of whole-body RT. In the first stage, participants performed 1 set of 10 to 15 repetitions in each of eight exercises, whereas in the second stage, they performed 2 sets of 10 to 15 repetitions. Body fat was estimated by DXA, while biochemical analyses were performed on venous blood samples collected in the morning hours after a 12 hours' fasting and after a minimum of 48 hours since the last physical exercise session. RESULTS: After the 24 weeks of RT, only G3x significantly reduced body fat mass (G2x=0.0%; G3x=-5.1%), whereas both G2x and G3x reduced blood glucose and C-reactive protein levels. Both groups improved HDL-C after the first 12-week stage compared to baseline, although the changes from pre- to post-training were not significantly different between groups. No significant difference was observed compared to baseline for total cholesterol, VLDL-C, LDL-C, and triglycerides for either group. CONCLUSIONS: These results suggest that RT-induced changes in health markers may occur regardless of RT frequency, whereas performing RT three times per week may be needed for reducing total body fat mass in older women.


Assuntos
Gorduras/metabolismo , Obesidade/terapia , Treinamento de Resistência , Tecido Adiposo/metabolismo , Idoso , Biomarcadores/sangue , Composição Corporal , Terapia por Exercício , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/sangue , Triglicerídeos/sangue
3.
Clin Sci (Lond) ; 134(8): 1031-1048, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32337536

RESUMO

Global trends in the prevalence of overweight and obesity put the adipocyte in the focus of huge medical interest. This review highlights a new topic in adipose tissue biology, namely the emerging pathogenic role of fat accumulation in bone marrow (BM). Specifically, we summarize current knowledge about the origin and function of BM adipose tissue (BMAT), provide evidence for the association of excess BMAT with diabetes and related cardiovascular complications, and discuss potential therapeutic approaches to correct BMAT dysfunction. There is still a significant uncertainty about the origins and function of BMAT, although several subpopulations of stromal cells have been suggested to have an adipogenic propensity. BM adipocytes are higly plastic and have a distinctive capacity to secrete adipokines that exert local and endocrine functions. BM adiposity is abundant in elderly people and has therefore been interpreted as a component of the whole-body ageing process. BM senescence and BMAT accumulation has been also reported in patients and animal models with Type 2 diabetes, being more pronounced in those with ischaemic complications. Understanding the mechanisms responsible for excess and altered function of BMAT could lead to new treatments able to preserve whole-body homeostasis.


Assuntos
Medula Óssea/metabolismo , Diabetes Mellitus/metabolismo , Gorduras/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Diabetes Mellitus/genética , Humanos
4.
Nat Commun ; 11(1): 1418, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184397

RESUMO

The Golgi apparatus plays a central role in the intracellular transport of macromolecules. However, molecular mechanisms of Golgi-mediated lipid transport remain poorly understood. Here, we show that genetic inactivation of the Golgi-resident protein GRASP55 in mice reduces whole-body fat mass via impaired intestinal fat absorption and evokes resistance to high-fat diet induced body weight gain. Mechanistic analyses reveal that GRASP55 participates in the Golgi-mediated lipid droplet (LD) targeting of some LD-associated lipases, such as ATGL and MGL, which is required for sustained lipid supply for chylomicron assembly and secretion. Consequently, GRASP55 deficiency leads to reduced chylomicron secretion and abnormally large LD formation in intestinal epithelial cells upon exogenous lipid challenge. Notably, deletion of dGrasp in Drosophila causes similar defects of lipid accumulation in the midgut. These results highlight the importance of the Golgi complex in cellular lipid regulation, which is evolutionary conserved, and uncover potential therapeutic targets for obesity-associated diseases.


Assuntos
Gorduras/metabolismo , Proteínas da Matriz do Complexo de Golgi/genética , Obesidade/genética , Obesidade/prevenção & controle , Animais , Transporte Biológico , Dieta Hiperlipídica , Drosophila , Complexo de Golgi/metabolismo , Proteínas da Matriz do Complexo de Golgi/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Obesidade/fisiopatologia , Ganho de Peso
6.
Proc Natl Acad Sci U S A ; 117(5): 2462-2472, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31953260

RESUMO

Preadipocytes can give rise to either white adipocytes or beige adipocytes. Owing to their distinct abilities in nutrient storage and energy expenditure, strategies that specifically promote "beiging" of adipocytes hold great promise for counterbalancing obesity and metabolic diseases. Yet, factors dictating the differentiation fate of adipocyte progenitors remain to be elucidated. We found that stearoyl-coenzyme A desaturase 1 (Scd1)-deficient mice, which resist metabolic stress, possess augmentation in beige adipocytes under basal conditions. Deletion of Scd1 in mature adipocytes expressing Fabp4 or Ucp1 did not affect thermogenesis in mice. Rather, Scd1 deficiency shifted the differentiation fate of preadipocytes from white adipogenesis to beige adipogenesis. Such effects are dependent on succinate accumulation in adipocyte progenitors, which fuels mitochondrial complex II activity. Suppression of mitochondrial complex II by Atpenin A5 or oxaloacetic acid reverted the differentiation potential of Scd1-deficient preadipocytes to white adipocytes. Furthermore, supplementation of succinate was found to increase beige adipocyte differentiation both in vitro and in vivo. Our data reveal an unappreciated role of Scd1 in determining the cell fate of adipocyte progenitors through succinate-dependent regulation of mitochondrial complex II.


Assuntos
Complexo II de Transporte de Elétrons/metabolismo , Gorduras/metabolismo , Obesidade/enzimologia , Estearoil-CoA Dessaturase/genética , Ácido Succínico/metabolismo , Adipócitos Bege/citologia , Adipócitos Bege/metabolismo , Adipogenia , Animais , Metabolismo Energético , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Estearoil-CoA Dessaturase/metabolismo , Termogênese
7.
Food Chem ; 306: 125560, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31590002

RESUMO

To control the oxidation in chicken fat by immobilized lipoxygenase (LOX), Maillard reaction products (MRPs) with chicken flavor were prepared and analyzed for flavor mechanism. >50% activity of immobilized LOX was retained after repeated use for five times or five weeks. The oxidized chicken fats were prepared by thermal, free LOX, and immobilized LOX treatments. After addition of chicken fats, Maillard reaction produced more aliphatic aldehydes and alcohols (126.0-839.5 ng/g and 493.5-2332.4 ng/g, respectively) which resulted in noticeable enhanced reaction, but the content of sulfur compounds such as thiols and thiophenes decreased significantly (870.8-1233.9 ng/g and 1125.0-2880.3 ng/g, respectively), and the structure of sulfur compounds could easily form alkyl side chains. However, there was no significant difference in sensory and flavors between oxidized chicken after treatments, which may be related to oxidized degree. The mechanism was proposed or aromatic effects of oxidized chicken fat on flaxseed derived MRPs.


Assuntos
Galinhas , Gorduras/metabolismo , Aromatizantes/química , Linho/química , Lipoxigenase/metabolismo , Animais , Enzimas Imobilizadas/metabolismo , Gorduras/química , Produtos Finais de Glicação Avançada/análise , Reação de Maillard , Oxirredução , Soja/enzimologia , Paladar
8.
Soft Matter ; 16(2): 289-306, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31840722

RESUMO

The reasons for the increased world-wide incidence of obesity, type-2 diabetes, and cardiovascular disease include sedentary lifestyles and poor food choices. Regulatory agencies in several countries now require companies to add unattractive front of package labels to their products where salt, sugar and fat (or saturated fat) levels are prominently displayed. After the demise of partially hydrogenated fats, saturated fat has become the new target. Consumption of saturated fat over polyunsaturated oil has been clearly shown to increase cholesterol levels in humans. However, saturated fats provide the functionality required in many food products. To complicate matters, concerns over sustainability, veganism, genetically modified organisms, animal welfare, as well as religious beliefs, severely limit our sources of saturated fat. In this review we will discuss recent advances in our understanding of the nano and mesoscale structure of fats, responsible for their physical functionality and contrast it to that of fat mimetics. Fat mimetics include polymeric networks of ethylcellulose, emulsion-templated networks of proteins and polysaccharides, colloidal and self-assembled fibrillar networks of polar lipid crystals, as well as solid o/w emulsions of oil trapped within crystallized lamellar mesophases. Clean label and economic considerations will also be touched upon.


Assuntos
Gorduras/química , Gorduras/metabolismo , Animais , Biomimética , Humanos
9.
J Agric Food Chem ; 67(51): 14110-14120, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31789033

RESUMO

Pentagalloyl glucose (PGG) has been studied for its valuable biological activities. However, the functional role of PGG in lipid metabolism in vivo is unclear. Here, we investigated the effects of PGG on lipid metabolism and its underlying mechanism in Caenorhabditis elegans. PGG decreased the accumulation of reactive oxygen species at 800 µM and remarkably increased the activities of antioxidant enzymes. PGG decreased significantly fat accumulation in wild-type worms (39.7 ± 5.7% in the normal group and 19.9 ± 4.5% in the high-fat group by Oil red O; 21.2 ± 2.7% in the high-fat group by Nile red; p < 0.001), but fat reduction by PGG was eliminated in the skn-1 mutant. The amount and size of lipid droplets in the ZXW618 mutant were decreased by PGG. The proportions of unsaturated fatty acids in both conditions were increased by PGG. In addition, the expression levels of fat metabolism genes were significantly changed in both conditions by PGG, which include mdt-15, pod-2, elo-2, fat-6, and fat-7 genes modulated fat synthesis; aak-2 and nhr-49 genes participated in fat consumption; and tub-1 gene regulated fat storage. However, fat-5 and acs-2 were downregulated in high-fat worms only, and vit-2 and lipl-4 were downregulated in normal worms only. Our study provided new insights into the role of PGG in alleviating fat accumulation and its underlying mechanism of action in C. elegans.


Assuntos
Caenorhabditis elegans/metabolismo , Gorduras/metabolismo , Taninos Hidrolisáveis/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Gotículas Lipídicas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
J Agric Food Chem ; 67(48): 13269-13281, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31725275

RESUMO

We studied the long-term influence of gestational diabetes mellitus (GDM) on the pancreas of offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on offspring's pancreas. GDM offspring were divided into three groups: GDM offspring, n-3 PUFA-adequate-GDM offspring, and n-3 PUFA-deficient GDM offspring. All healthy and GDM offspring were fed up to 11 months old. The pancreas of GDM offspring exhibited fatty infiltration at 11 months old, whereas n-3 PUFA improved the pancreatic fatty infiltration. n-3 PUFA lowered the pancreatic oxidative stress and inflammation. Surprisingly, n-3 PUFA postponed pancreatic telomere shortening of GDM offspring at old age. Nontargeted metabolomics showed that many metabolites were altered in the pancreas of GDM offspring at old age, including l-valine, ceramide, acylcarnitines, tocotrienol, cholesteryl acetate, and biotin. n-3 PUFA modulated some altered metabolites and metabolic pathways. Therefore, GDM caused the long-term effects on offspring's pancreas, whereas n-3 PUFA played a beneficial role.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Pâncreas/metabolismo , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Animais , Diabetes Gestacional/metabolismo , Gorduras/metabolismo , Feminino , Humanos , Masculino , Metabolômica , Pâncreas/química , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Wistar , Telômero/metabolismo
11.
Eur J Appl Physiol ; 119(11-12): 2711-2722, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31673759

RESUMO

PURPOSE: We aimed to investigate if hereditary factors, leisure-time physical activity (LTPA) and metabolic health interact with resting fat oxidation (RFO) and peak fat oxidation (PFO) during ergometer cycling. METHODS: We recruited 23 male monozygotic twin pairs (aged 32-37 years) and determined their RFO and PFO with indirect calorimetry for 21 and 19 twin pairs and for 43 and 41 twin individuals, respectively. Using physical activity interviews and the Baecke questionnaire, we identified 10 twin pairs as LTPA discordant for the past 3 years. Of the twin pairs, 8 pairs participated in both RFO and PFO measurements, and 2 pairs participated in either of the measurements. We quantified the participants' metabolic health with a 2-h oral glucose tolerance test. RESULTS: Fat oxidation within co-twins was correlated at rest [intraclass correlation coefficient (ICC) = 0.54, 95% confidence interval (CI) 0.15-0.78] and during exercise (ICC = 0.67, 95% CI 0.33-0.86). The LTPA-discordant pairs had no pairwise differences in RFO or PFO. In the twin individual-based analysis, PFO was positively correlated with the past 12-month LTPA (r = 0.26, p = 0.034) and the Baecke score (r = 0.40, p = 0.022) and negatively correlated with the area under the curve of insulin (r = - 0.42, p = 0.015) and glucose (r = - 0.31, p = 0.050) during the oral glucose tolerance test. CONCLUSIONS: Hereditary factors were more important than LTPA for determining fat oxidation at rest and during exercise. Additionally, PFO, but not RFO, was associated with better metabolic health.


Assuntos
Exercício Físico/fisiologia , Gorduras/metabolismo , Atividade Motora/fisiologia , Descanso/fisiologia , Adiposidade/fisiologia , Adulto , Calorimetria Indireta/métodos , Teste de Tolerância a Glucose/métodos , Humanos , Masculino , Oxirredução , Gêmeos Monozigóticos , Adulto Jovem
12.
BMC Complement Altern Med ; 19(1): 294, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684925

RESUMO

BACKGOUND: Obesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFLD is the most common liver disease and is rapidly becoming a global public health problem. Maoberry (Antidesma bunius) is a fruit rich in antioxidants, especially phenolic compounds, which are reported to have benefits for patients with NAFLD. METHODS: We evaluated the effect of Maoberry extract on fat metabolism in liver tissues of high fat diet-induced rats. Five (5) groups (n = 12) of male Sprague-Dawley (SD) rats were divided into those given a high fat diet with no treatment (HF), different dosages of Maoberry extracts (0.38 [ML], 0.76 [MM) and 1.52 [MH] g/kg body weight) and 10 mg/kg statin (STAT). The rats were fed a high fat diet for 4 weeks to induce obesity and subsequently continued more for 12 weeks with treatments of Maoberry extracts or STAT. The levels of triglyceride, liver enzymes, oxidative stress and inflammation markers, triglyceride synthesis regulators, and pathology of the liver in high fat diet-induced rats were investigated. RESULTS: Feeding Maoberry extract in MH groups resulted in decreasing levels of serum alanine aminotransferase (ALT), liver triglyceride, liver thiobarbituric acid reactive substances (TBARS) and mRNA expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, glycerol-3-phosphate acyltransferase (GPAT)-1 and acetyl-coenzyme A carboxylase (ACC) compared with the HF group (P < 0.05). Moreover, histopathological study of the liver showed reduced fat droplets in the Maoberry extract treatment groups, especially in MH groups and STAT treatment groups. CONCLUSIONS: The improvements of fat metabolism in liver tissues of rats fed a high-fat diet were observed in Maoberry extracts treatment groups. The underline mechanism that link to fat metabolism might be through the process accompanied with down-regulated the gene expression of key enzymes of lipid production, antioxidant activity, and anti-inflammation properties of Maoberry extracts which contains high levels of phenolic and flavonoid compounds.


Assuntos
Antioxidantes/administração & dosagem , Gorduras/metabolismo , Fígado/efeitos dos fármacos , Malpighiales/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Acetil-CoA C-Acetiltransferase/genética , Acetil-CoA C-Acetiltransferase/metabolismo , Animais , Antioxidantes/química , Dieta Hiperlipídica/efeitos adversos , Frutas/química , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
13.
Am J Clin Nutr ; 110(6): 1275-1286, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31535135

RESUMO

BACKGROUND: Emerging data suggest that weight gain is associated with changes in neural response to palatable food tastes and palatable food cues, which may serve to maintain overeating. OBJECTIVE: We investigated whether weight gain is associated with neural changes in response to tastes of milkshakes varying in fat and sugar content and palatable food images. METHODS: We compared changes in neural activity between initially healthy-weight adolescents who gained weight (n = 36) and those showing weight stability (n = 31) over 2-3 y. RESULTS: Adolescents who gained weight compared with those who remained weight stable showed decreases in activation in the postcentral gyrus, prefrontal cortex, insula, and anterior cingulate cortex, and increases in activation in the parietal lobe, posterior cingulate cortex, and inferior frontal gyrus in response to a high-fat/low-sugar compared with low-fat/low-sugar milkshake. Weight gainers also showed greater decreases in activation in the anterior insula and lateral orbitofrontal cortex in response to a high-fat/high-sugar compared with low-fat/low-sugar milkshake than those who remained weight stable. No group differences emerged in response to a low-fat/high-sugar compared with a low-fat/low-sugar milkshake. Weight gainers compared with those who remained weight stable showed greater decreases in activation in the middle temporal gyrus and increases in cuneus activation in response to appetizing compared with unappetizing food pictures. The significant interactions were partially driven by group differences in baseline responsivity and by opposite changes in neural activation in adolescents who remained weight stable. CONCLUSIONS: Data suggest that weight gain is associated with a decrease in responsivity of regions associated with taste and reward processing to palatable high-fat- and high-fat/high-sugar food tastes. Data also suggest that avoiding weight gain increases taste sensitivity, which may prevent future excessive weight gain.This trial was registered at clinicaltrials.gov as NCT01949636.


Assuntos
Encéfalo/diagnóstico por imagem , Gorduras/metabolismo , Sobrepeso/psicologia , Açúcares/metabolismo , Percepção Gustatória , Ganho de Peso , Adolescente , Encéfalo/fisiopatologia , Mapeamento Encefálico , Ingestão de Alimentos , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Sobrepeso/diagnóstico por imagem , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia
14.
J Agric Food Chem ; 67(37): 10513-10520, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31475823

RESUMO

Amino acids can stimulate milk fat synthesis, but the underlying molecular mechanism is still largely unknown. In this study, we studied the regulatory role and corresponding molecular mechanism of cAMP response element-binding protein-regulated transcription coactivator 2 (CRTC2) in amino acid-induced milk fat synthesis in mammary epithelial cells. We showed that leucine and methionine stimulated CRTC2 but not p-CRTC2(Ser171) expression and nuclear localization in cow mammary epithelial cells. Knockdown of CRTC2 decreased milk fat synthesis and sterol regulatory element binding protein 1c (SREBP-1c) expression and activation, whereas its overexpression had the opposite effects. Neither knockdown nor overexpression of CRTC2 affected ß-casein synthesis and phosphorylation of the machanistic target of rapamycin (mTOR), suggesting that CRTC2 only regulates milk fat synthesis. CRTC2 knockdown abolished the stimulation of leucine and methionine on SREBP-1c expression and activation. Knockdown or overexpression of CRTC2 did not affect the protein level of cAMP-response element-binding protein (CREB) and its phosphorylation but decreased or increased the binding of p-CREB to the promoter of SREBP-1c gene and its mRNA expression, respectively. Mutation of Ser171 of CRTC2 did not alter the stimulation of CRTC2 on SREBP-1c expression and activation, further suggesting that CRTC2 functions in the nucleus. mTOR inhibition by rapamycin totally blocked the stimulation of leucine and methionine on CRTC2 expression. The expression of CRTC2 was dramatically higher in the mouse mammary gland of lactation period, compared with that of the dry and puberty periods, whereas p-CRTC2(Ser171) was not changed, further supporting that CRTC2 is a key transcription coactivator for milk fat synthesis. These results uncover that CRTC2 is a key transcription coactivator of amino acid-stimulated mTOR-mediated milk fat synthesis in mammary epithelial cells.


Assuntos
Aminoácidos/metabolismo , Bovinos/metabolismo , Células Epiteliais/metabolismo , Gorduras/metabolismo , Glândulas Mamárias Animais/citologia , Leite/metabolismo , Fatores de Transcrição/metabolismo , Animais , Bovinos/genética , Feminino , Glândulas Mamárias Animais/metabolismo , Camundongos , Fosforilação , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética
15.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(12): 158528, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31520776

RESUMO

Ribosomal protein L8 (RPL8) was considered as a promising candidate gene for the milk fat percentage trait in dairy cattle in our previous genome-wide association studies, but the mechanism remains to be determined. Here we investigated the molecular mechanism underlying the effect of bovine RPL8 on milk fat percentage. We demonstrated that RPL8 silencing in bovine mammary epithelial cells affected the expression of genes encoding fat-related enzymes (ACACA, FASN, ACSS1, FABP3, SREBP-1, DGAT1, GPAM, PLIN2, PLIN5 and CIDEA). Furthermore, we showed here that a single nucleotide polymorphism, g.-931G > T (chr14:1508300, UMD3.1) in the putative RPL8 promoter region significantly reduced its promoter activity. Interestingly, this decrease in activity was paralleled by lower RPL8 expression in mammary gland tissues of dairy cattle with the homozygous TT genotype compared to that of cattle with the wild-type homozygous GG genotype. Importantly, we found g.-931G > T added a paired box 6 (Pax6)-binding site and this mutation located in the presumed Pax6-binding site. EMSA and co-immunoprecipitation (Co-IP) assays confirmed the interaction between RPL8 and Pax6 and the T allele exhibited a higher affinity of DNA/protein interactions than G allele, suggesting that Pax6 is an important transcription factor for RPL8 expression. In addition, lactating cows with the GG and GT genotypes presented a significant decrease in milk fat percentage compared to cows with TT genotypes. Altogether, our study indicated that g.-931G > T at RPL8 promoter altered its expression by affecting the interplay between Pax6 and RPL8, which may account for the association with milk fat traits. Findings herein first elucidated the biological function of RPL8 gene in milk fat and the identified SNP g.-931G > T may be considered as genetic makers for breeding in dairy cattle.


Assuntos
Bovinos/genética , Gorduras/metabolismo , Leite/metabolismo , Fator de Transcrição PAX6/metabolismo , Proteínas Ribossômicas/genética , Animais , Bovinos/metabolismo , Regulação para Baixo , Gorduras/química , Feminino , Lactação , Leite/química , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Ribossômicas/metabolismo , Ativação Transcricional
16.
FEBS Open Bio ; 9(9): 1623-1631, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31368651

RESUMO

In environments with limited food and high population density, Caenorhabditis elegans larvae may enter the dauer stage, in which metabolism is shifted to fat accumulation to allow larvae to survive for months without food. Mutations in the insulin-like receptor gene daf-2 force C. elegans to constitutively form dauer larva at higher temperature. It has been reported that autophagy is required for fat accumulation in daf-2 dauer larva. However, the mechanism underlying this process remains unknown. Here, we report that autophagy gene atg-18 acts in a cell nonautonomous manner in neurons and intestinal cells to mediate the influence of daf-2 signaling on fat metabolism. Moreover, ATG-18 in chemosensory neurons plays a vital role in this metabolic process. Finally, we report that neuronal ATG-18 functions through neurotransmitters to control fat storage in daf-2 dauers, which suggests an essential role of autophagy in the neuroendocrine regulation of fat metabolism by insulin-like signaling.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Gorduras/metabolismo , Larva/metabolismo , Proteínas de Membrana/metabolismo , Sistemas Neurossecretores/metabolismo , Animais , Proteínas Relacionadas à Autofagia/genética , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Larva/genética , Proteínas de Membrana/genética
17.
J Agric Food Chem ; 67(32): 8725-8734, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31295997

RESUMO

Texture perception is conceptualized as an emergent cognitive response to food characteristics that comprise several physical and chemical properties. Contemporary oral processing research focuses on revealing the relationship between the sensory perceptions and food properties, with the goal of enabling rational product design. One major challenge is associated with revealing the complex molecular and biocolloidal interactions underpinning even simple texture percepts. Here, we introduce in vitro oral processing, which considers oral processing in terms of discrete units of operation (first bite, comminution, granulation, bolus formation, and tribology). Within this framework, we systematically investigate the material properties that govern each specific oral processing unit operation without being impacted by the biological complexity of the oral environment. We describe how this framework was used to rationally design a low-fat potato chip with improved sensory properties by investigating the impact from adding back, to a low-fat potato chip, a small amount of oil mixed with the surface-active agent polyglycerol polyricinoleate (PGPR). The relevance of instrumental measures is validated by sensory assessment, whereby panelists ranked the perceived oiliness of three different types of potato chips. The sensory results indicate that perceived oiliness was higher when a low-fat potato chip was supplemented with an additional 0.5% (w/w) topical coating (the coating comprised 15%, w/w, PGPR in oil) compared to the unaltered low-fat potato chip. The perceived difference in oiliness is hypothesized to correspond to the dynamic friction measured in vitro with a saliva-coated substrate in the presence and absence of PGPR. The study illustrates how dividing oral processing into distinct units provides a rational approach to food product design focused on controlling key sensory attributes.


Assuntos
Gorduras/análise , Boca/metabolismo , Solanum tuberosum/metabolismo , Gorduras/metabolismo , Manipulação de Alimentos , Humanos , Modelos Biológicos , Reologia , Saliva/metabolismo , Lanches , Solanum tuberosum/química
18.
J Agric Food Chem ; 67(31): 8485-8492, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31304752

RESUMO

How short-chain fatty acids (FAs) affect cell membrane morphology and milk fat biosynthesis in mammary epithelial cells (MECs) is yet unclear. This study investigated the primary bovine MEC response to different FAs. We observed that the cell surface ultrastructures were influenced by chain length and degree of saturability of FAs. The CD36, FATP1, and FABP3 gene expression was affected independent of the type of FA. FASN, LPIN1, PPARα, and PPARγ transcripts were more sensitive to the short-chain FAs (acetic and ß-hydroxybutyric acids). Furthermore, short-chain FAs inclined to regulate FA degradation-, elongation-, and metabolism-associated pathways, while long-chain FAs (stearic and trans-10,cis-12 conjugated linolenic acids) modulated extracellular matrix-receptor interaction-, transcriptional misregulation-, microRNA-, and ribosome biogenesis-related pathways. However, triacylglycerol accumulation in the cytoplasm was not changed by all of the FAs. Overall, FAs with different chain lengths and degrees of saturability could differentially alter primary bovine MEC cell morphology and influence protein profiles involved in milk fat synthesis pathways.


Assuntos
Bovinos/metabolismo , Células Epiteliais/metabolismo , Gorduras/metabolismo , Ácidos Graxos não Esterificados/química , Ácidos Graxos não Esterificados/metabolismo , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , Animais , Antígenos CD36/genética , Antígenos CD36/metabolismo , Bovinos/genética , Gorduras/química , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Feminino , Glândulas Mamárias Animais/citologia , Leite/química , PPAR alfa/genética , PPAR alfa/metabolismo , Triglicerídeos/metabolismo
19.
J Dairy Sci ; 102(9): 8417-8422, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301848

RESUMO

The objective of this study was to evaluate the accuracy of inline milk fat-to-protein (F:P) data to detect hyperketonemia (HYK) in herds with automated milking systems (AMS). The F:P ratio has been investigated as a tool for detecting HYK with moderate accuracy in past studies, but inline F:P data in AMS may also be useful for HYK screening. To assess the accuracy of these data in commercial settings, we monitored 484 cows from 9 AMS herds for their first 3 wk of lactation, taking blood samples once per week (n = 1,427). Positive cases of HYK were defined by whole-blood ß-hydroxybutyrate (BHB) concentrations ≥1.2 or ≥1.4 mmol/L. Milk data were collected from the AMS software on each farm for each cow and converted into 4 different F:P values: (1) value from the same day as the BHB test; (2) 5-d centered-moving average (CMA); (3) 5-d backward-moving average (BMA); (4) 5-d forward-moving average (FMA). In linear regression models, all 4 values were associated with BHB, but slope estimates varied and R2 were low: same day (slope = 0.95, R2 = 0.07), CMA (slope = 1.05, R2 = 0.07), BMA (slope = 0.65, R2 = 0.04), and FMA (slope = 1.23, R2 = 0.09). In logistic regression models, the odds of having HYK (BHB ≥1.2 mmol/L) increased with every 0.1-unit increase from the mean F:P ratio (1.16) using same-day values (odds ratio = 1.35, 95% confidence interval = 1.25-1.47) and CMA (odds ratio = 1.39, 95% confidence interval = 1.27-1.51). The same increase in F:P from mean BMA (1.14) and FMA (1.17) was associated with 1.22 and 1.49 times the odds of HYK, respectively. For all 4 F:P variations, we evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of different F:P thresholds with HYK status. As the F:P threshold increased from 1.17 to 1.50, sensitivity decreased (range: 77 to 9%) but specificity increased (range: 58 to 96%). Same-day and CMA F:P cutoffs at which a balance was reached between sensitivity and specificity ranged from 1.18 to 1.22; however, even at these values we found high rates of false positives and negatives (range: 31-39%). These results suggest that inline milk F:P data from inconsistently calibrated sensors should not be used alone to detect HYK in AMS herds.


Assuntos
Doenças dos Bovinos/diagnóstico , Gorduras/metabolismo , Cetose/veterinária , Proteínas do Leite/metabolismo , Leite/metabolismo , Ácido 3-Hidroxibutírico/sangue , Animais , Automação , Bovinos , Doenças dos Bovinos/sangue , Indústria de Laticínios/métodos , Feminino , Cetose/sangue , Cetose/diagnóstico , Lactação , Modelos Lineares , Modelos Logísticos , Sensibilidade e Especificidade
20.
Food Funct ; 10(8): 4966-4974, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31343008

RESUMO

trans-Trismethoxy resveratrol (TMR) is a methyl analog of resveratrol. It is found to exhibit enhanced biological effects compared to resveratrol, such as inhibition of cancer cell growth and pro-apoptotic activities. However, the role of TMR in lipid metabolism is not fully understood. In this study, we used Caenorhabditis elegans, an in vivo nematode model which has been widely applied in disease research, including research on obesity, to investigate the effect of TMR on lipid metabolism. Treatment with TMR (100 and 200 µM) for 4 days significantly reduced triglyceride accumulation (14% and 20% reduction over the control, respectively) of C. elegans, without affecting nematode growth, food intake and reproduction. Treatment with TMR significantly downregulated stearoyl-CoA desaturase genes, fat-6 and fat-7, accompanied by a decrease in the desaturation index of fatty acids, the ratio of oleic acid to stearic acid. These results suggest that TMR inhibits fat accumulation by downregulating stearoyl-CoA desaturase in C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Gorduras/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Resveratrol/farmacologia , Estearoil-CoA Dessaturase/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Ácidos Graxos Dessaturases/genética , Resveratrol/química , Estearoil-CoA Dessaturase/genética , Triglicerídeos/metabolismo
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