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1.
Nutrients ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371851

RESUMO

Diet-induced obesity reduces dopaminergic neurotransmission in the nucleus accumbens (NAc), and stressful weight loss interventions could promote cravings for palatable foods high in fat and sugar that stimulate dopamine. Activation of κ-opioid receptors (KORs) reduces synaptic dopamine, but contribution of KORs to lower dopamine tone after dietary changes is unknown. Therefore, the purpose of this study was to determine the function of KORs in C57BL/6 mice that consumed a 60% high-fat diet (HFD) for six weeks followed by replacement of HFD with a control 10% fat diet for one day or one week. HFD replacement induced voluntary caloric restriction and weight loss. However, fast-scan cyclic voltammetry revealed no differences in baseline dopamine parameters, whereas sex effects were revealed during KOR stimulation. NAc core dopamine release was reduced by KOR agonism after one day of HFD replacement in females but after one week of HFD replacement in males. Further, elevated plus-maze testing revealed no diet effects during HFD replacement on overt anxiety. These results suggest that KORs reduce NAc dopamine tone and increase food-related anxiety during dietary weight loss interventions that could subsequently promote palatable food cravings and inhibit weight loss.


Assuntos
Dieta com Restrição de Gorduras/métodos , Dopamina/metabolismo , Núcleo Accumbens/metabolismo , Obesidade/metabolismo , Receptores Opioides kappa/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/farmacologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Transmissão Sináptica/efeitos dos fármacos
2.
Nutrients ; 13(8)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34444773

RESUMO

Structural differences in dietary fatty acids modify their rate of oxidation and effect on satiety, endpoints that may influence the development of obesity. This study tests the hypothesis that meals containing fat sources with elevated unsaturated fats will result in greater postprandial energy expenditure, fat oxidation, and satiety than meals containing fats with greater saturation. In a randomized, 5-way crossover design, healthy men and women (n = 23; age: 25.7 ± 6.6 years; BMI: 27.7 ± 3.8 kg/m2) consumed liquid meals containing 30 g of fat from heavy cream (HC), olive oil (OO), sunflower oil (SFO), flaxseed oil (FSO), and fish oil (FO). Energy expenditure and diet-induced thermogenesis (DIT) were determined by metabolic rate over a 240 min postprandial period. Serum concentrations of ghrelin, glucose, insulin, and triacylglycerol (TAG) were assessed. DIT induced by SFO was 5% lower than HC and FO (p = 0.04). Energy expenditure and substrate oxidation did not differ between fat sources. Postprandial TAG concentrations were significantly affected by fat source (p = 0.0001). Varying fat sources by the degree of saturation and PUFA type modified DIT but not satiety responses in normal to obese adult men and women.


Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos/farmacologia , Saciação/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Adolescente , Adulto , Estudos Cross-Over , Metabolismo Energético/efeitos dos fármacos , Gorduras/química , Gorduras/metabolismo , Gorduras/farmacologia , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Insaturados/química , Feminino , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Obesidade/metabolismo , Azeite de Oliva/farmacologia , Oxirredução , Período Pós-Prandial/efeitos dos fármacos , Resposta de Saciedade/efeitos dos fármacos , Adulto Jovem
3.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063748

RESUMO

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.


Assuntos
Acilação/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , N-Acetilglucosaminiltransferases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/metabolismo , Células Clonais , Dieta Hiperlipídica/efeitos adversos , Hepatócitos/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Morfolinas/farmacologia , Ácido Oleico/farmacologia , Fosforilação/efeitos dos fármacos , Piperidinas/farmacologia , Ribonucleotídeos/metabolismo
4.
Food Chem ; 361: 130160, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062457

RESUMO

The quality of crustaceans' flesh has direct impact on consumers' purchase choices, with water environment and dietary nutrition being effective ways to regulate flesh quality. The aim of present study was to investigate the impacts of water salinity (low, 4 and medium, 23) and dietary lipid source (fish oil and soybean oil) on nutritional values, texture, taste and odor of flesh of mud crab. While water salinity had no significant influence on nutritional values of crab flesh, crabs fed soybean oil displayed significantly lower contents of amino acids and n-3 PUFAs in muscle. However, crabs reared at low salinity showed reduced flesh hardness, chewiness and gumminess likely related to altered myofiber structure, that impacted muscle texture. Furthermore, low salinity and dietary soybean oil weakened umami taste and aroma characteristics of crab flesh associated with decreased contents of free amino acids, flavor nucleotides, inorganic ions and odor active compounds in flesh.


Assuntos
Ração Animal , Aquicultura/métodos , Braquiúros/química , Frutos do Mar/análise , Aminoácidos/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Gorduras na Dieta/farmacologia , Óleos de Peixe/farmacologia , Qualidade dos Alimentos , Valor Nutritivo , Salinidade , Proteínas de Frutos do Mar/análise , Óleo de Soja/farmacologia , Paladar , Compostos Orgânicos Voláteis/análise
5.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065436

RESUMO

High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.


Assuntos
Aminopeptidases/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Córtex Renal/efeitos dos fármacos , Medula Renal/efeitos dos fármacos , Azeite de Oliva/farmacologia , Animais , Manteiga , Colesterol/metabolismo , Dieta Mediterrânea , Gorduras na Dieta/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Córtex Renal/metabolismo , Medula Renal/metabolismo , Masculino , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/efeitos dos fármacos
6.
Nutrients ; 13(6)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072137

RESUMO

Dietary fatty acids (DFAs) play key roles in different metabolic processes in humans and other mammals. DFAs have been considered beneficial for health, particularly polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs). Additionally, microRNAs (miRNAs) exert their function on DFA metabolism by modulating gene expression, and have drawn great attention for their potential as biomarkers and therapeutic targets. This review explicitly examined the effects of DFAs on miRNA expression associated with metabolic diseases, such as obesity, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD), as well as inflammation, published in the last ten years. DFAs have been shown to induce and repress miRNA expression associated with metabolic disease and inflammation in different cell types and organisms, both in vivo and in vitro, depending on varying combinations of DFAs, doses, and the duration of treatment. However, studies are limited and heterogeneous in methodology. Additionally, recent studies demonstrated that high fat ketogenic diets, many enriched with saturated fats, do not increase serum saturated fat content in humans, and are not associated with increased inflammation. Thus, these findings shed light on the complexity of novel treatment and DFA interventions for metabolic disease and to maintain health. Further studies are needed to advance molecular therapeutic approaches, including miRNA-based strategies in human health and disease.


Assuntos
Gorduras na Dieta/farmacologia , Inflamação/metabolismo , Doenças Metabólicas/metabolismo , MicroRNAs , Animais , Ácidos Graxos/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , MicroRNAs/análise , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos
7.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063366

RESUMO

The high-fat, low-carbohydrate (ketogenic) diet has grown in popularity in the last decade as a weight loss tool. Research into the diet's effects on the body have revealed a variety of other health benefits. The use of exogenous ketone supplements to confer the benefits of the diet without strict adherence to it represents an exciting new area of focus. Synthetic ketogenic compounds are of particular interest that has received very little emphasis and is an untapped area of focus for chemical synthesis. In this review, we summarize the chemical basis for ketogenicity and opportunities for further advancement of the field.


Assuntos
Dieta Cetogênica , Suplementos Nutricionais , Corpos Cetônicos , Dieta Cetogênica/história , Gorduras na Dieta/farmacologia , Metabolismo Energético , Epilepsia/dietoterapia , Glicólise , História Antiga , Humanos , Corpos Cetônicos/metabolismo , Cetose/induzido quimicamente
8.
Nutrients ; 13(5)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064496

RESUMO

The health effects of saturated fat, particularly tropical oil, on cardiovascular disease are unclear. We investigated the effect of tropical oil (palm and coconut oils), lard, and other common vegetable oils (soybean and rice bran oils) that are widely used in tropical and Asian countries on lipid profiles. We performed an umbrella review of meta-analyses and systematic reviews. Electronic databases (Medline, Scopus, Embase, and Cochrane) were searched up to December 2018 without language restriction. We identified nine meta-analyses that investigated the effect of dietary oils on lipid levels. Replacement of polyunsaturated fatty-acid-rich oils (PUFAs) and monounsaturated FA-rich oils (MUFAs) with palm oil significantly increased low-density lipoprotein cholesterol (LDL-c), by 3.43 (0.44-6.41) mg/dL and 9.18 (6.90-11.45) mg/dL, respectively, and high-density lipoprotein cholesterol (HDL-c), by 1.89 (1.23-2.55) mg/dL and 0.94 (-0.07-1.97) mg/dL, respectively. Replacement of PUFAs with coconut oil significantly increased HDL-c and total cholesterol -by 2.27 (0.93-3.6) mg/dL and 5.88 (0.21-11.55) mg/dL, respectively-but not LDL-c. Substituting lard for MUFAs and PUFAs increased LDL-c-by 8.39 (2.83-13.95) mg/dL and 9.85 (6.06-13.65) mg/dL, respectively-but not HDL-c. Soybean oil substituted for other PUFAs had no effect on lipid levels, while rice bran oil substitution decreased LDL-c. Our findings show the deleterious effect of saturated fats from animal sources on lipid profiles. Replacement of unsaturated plant-derived fats with plant-derived saturated fats slightly increases LDL-c but also increases HDL-c, which in turn may exert a neutral effect on cardiovascular health.


Assuntos
Doenças Cardiovasculares/etiologia , Óleo de Coco/farmacologia , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos/farmacologia , Óleo de Palmeira/farmacologia , Animais , Ásia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Ingestão de Alimentos/fisiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Metanálise como Assunto , Óleos Vegetais/farmacologia , Óleo de Farelo de Arroz/farmacologia , Óleo de Soja/farmacologia , Revisões Sistemáticas como Assunto , Clima Tropical
9.
J Nutr Biochem ; 95: 108764, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33964465

RESUMO

Obesity-associated inflammation in white adipose tissue (WAT) is a causal factor of systemic insulin resistance. To better understand how adipocytes regulate WAT inflammation, the present study generated chimeric mice in which inducible 6-phosphofructo-2-kinase was low, normal, or high in WAT while the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Pfkfb3) was normal in hematopoietic cells, and analyzed changes in high-fat diet (HFD)-induced WAT inflammation and systemic insulin resistance in the mice. Indicated by proinflammatory signaling and cytokine expression, the severity of HFD-induced WAT inflammation in WT â†’ Pfkfb3+/- mice, whose Pfkfb3 was disrupted in WAT adipocytes but not hematopoietic cells, was comparable with that in WT â†’ WT mice, whose Pfkfb3 was normal in all cells. In contrast, the severity of HFD-induced WAT inflammation in WT â†’ Adi-Tg mice, whose Pfkfb3 was over-expressed in WAT adipocytes but not hematopoietic cells, remained much lower than that in WT â†’ WT mice. Additionally, HFD-induced insulin resistance was correlated with the status of WAT inflammation and comparable between WT â†’ Pfkfb3+/- mice and WT â†’ WT mice, but was significantly lower in WT â†’ Adi-Tg mice than in WT â†’ WT mice. In vitro, palmitoleate decreased macrophage phosphorylation states of Jnk p46 and Nfkb p65 and potentiated the effect of interleukin 4 on suppressing macrophage proinflammatory activation. Taken together, these results suggest that the Pfkfb3 in adipocytes functions to suppress WAT inflammation. Moreover, the role played by adipocyte Pfkfb3 is attributable to, at least in part, palmitoleate promotion of macrophage anti-inflammatory activation.


Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Inflamação/metabolismo , Macrófagos/fisiologia , Fosfofrutoquinase-2/metabolismo , Adipócitos Brancos/metabolismo , Transferência Adotiva , Animais , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Ácidos Graxos Monoinsaturados/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Intolerância à Glucose , Resistência à Insulina , Masculino , Camundongos , Fosfofrutoquinase-2/genética , Transdução de Sinais
10.
J Nutr Biochem ; 95: 108762, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33965534

RESUMO

The physiological functions of the aryl hydrocarbon receptor (AHR) are only beginning to unfold. Studies in wildtype and AHR knockout (AHRKO) mice have recently disclosed that AHR activity is required for obesity and steatohepatitis to develop when mice are fed with a high-fat diet (HFD). In addition, a line of AHRKO mouse has been reported to accumulate retinoids in the liver. Whether these are universal manifestations across species related to AHR activity level is not known yet. Therefore, we here subjected wildtype and AHRKO male rats (on Sprague-Dawley background) to HFD feeding coupled with free access to 10% sucrose solution and water; controls received a standard diet and water. Although the HFD-fed rats consumed more energy throughout the 24-week feeding regimen, they did not get overweight. However, relative weights of the brown and epididymal adipose tissues were elevated in HFD-fed rats, while that of the liver was lower in AHRKO than wildtype rats. Moreover, the four groups exhibited diet- or genotype-dependent differences in biochemical variables, some of which suggested marked dissimilarities from AHRKO mice. Expression of pro- and anti-inflammatory genes was induced in livers of HFD-fed AHRKO rats, but histologically they did not differ from others. HFD reduced the hepatic concentrations of retinyl palmitate, 9-cis-4-oxo-13,14-dihydroretinoic acid and (suggestively) retinol, whereas AHR status had no effect. Hence, the background strain/line of AHRKO rat is resistant to diet-induced obesity, and AHR does not modulate this or liver retinoid concentrations. Yet, subtle AHR-dependent differences in energy balance-related factors exist despite similar weight development.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/farmacologia , Metabolismo Energético/efeitos dos fármacos , Fígado/química , Receptores de Hidrocarboneto Arílico/deficiência , Retinoides/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Deleção de Genes , Genótipo , Fígado/metabolismo , Fígado/patologia , Masculino , Tamanho do Órgão , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/metabolismo , Retinoides/química
11.
Nutrients ; 13(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808927

RESUMO

Vegetable oils such as palm oil (enriched in saturated fatty acids, SFA) and high-oleic-acid sunflower oil (HOSO, containing mainly monounsaturated fatty acids, MUFA) have emerged as the most common replacements for trans-fats in the food industry. The aim of this study is to analyze the impact of SFA and MUFA-enriched high-fat (HF) diets on endothelial function, vascular remodeling, and arterial stiffness compared to commercial HF diets. Five-week-old male C57BL6J mice were fed a standard (SD), a HF diet enriched with SFA (saturated oil-enriched Food, SOLF), a HF diet enriched with MUFA (unsaturated oil-enriched Food, UOLF), or a commercial HF diet for 8 weeks. Vascular function was analyzed in the thoracic aorta. Structural and mechanical parameters were assessed in mesenteric arteries by pressure myography. SOLF, UOLF, and HF diet reduced contractile responses to phenylephrine and induced endothelial dysfunction in the thoracic aorta. A significant increase in the ß-index, and thus in arterial stiffness, was also detected in mesenteric arteries from the three HF groups, due to enhanced deposition of collagen in the vascular wall. SOLF also induced hypotrophic inward remodeling. In conclusion, these data demonstrate a deleterious effect of HF feeding on obesity-related vascular alterations that is exacerbated by SFA.


Assuntos
Artérias/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Rigidez Vascular/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Artérias/fisiologia , Peso Corporal , Colágeno/metabolismo , Dieta Hiperlipídica , Gorduras Insaturadas na Dieta/farmacologia , Elastina , Ácidos Graxos/farmacologia , Distrofia Endotelial de Fuchs , Glucose/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Ácido Oleico , Óleos Vegetais , Óleo de Girassol , Remodelação Vascular/efeitos dos fármacos
12.
J Nutr Biochem ; 93: 108620, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33705944

RESUMO

Many of the metabolic effects evoked by the ketogenic diet mimic the actions of fasting and the benefits of the ketogenic diet are often attributed to these similarities. Since fasting is a potent autophagy inductor in vivo and in vitro it has been hypothesized that the ketogenic diet may upregulate autophagy. The aim of the present study was to provide a comprehensive evaluation of the influence of the ketogenic diet on the hepatic autophagy. C57BL/6N male mice were fed with two different ketogenic chows composed of fat of either animal or plant origin for 4 weeks. To gain some insight into the time frame for the induction of autophagy on the ketogenic diet, we performed a short-term experiment in which animals were fed with ketogenic diets for only 24 or 48 h. The results showed that autophagy is upregulated in the livers of animals fed with the ketogenic diet. Moreover, the size of the observed effect was likely dependent on the diet composition. Subsequently, the markers of regulatory pathways that may link ketogenic diet action to autophagy were measured, i.e., the activity of mTORC1, activation of AMPK, and the levels of SIRT1, p53, and FOXO3. Overall, observed treatment-specific effects including the upregulation of SIRT1 and downregulation of FOXO3 and p53. Finally, a GC/MS analysis of the fatty acid composition of animals' livers and the chows was performed in order to obtain an idea about the presence of specific compounds that may shape the effects of ketogenic diets on autophagy.


Assuntos
Autofagia/fisiologia , Dieta Cetogênica , Gorduras na Dieta/farmacologia , Cetose/metabolismo , Fígado/fisiologia , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Gorduras na Dieta/análise , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plantas , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Am J Physiol Endocrinol Metab ; 320(4): E808-E821, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33682458

RESUMO

Exercise improves obesity-induced insulin resistance and metabolic disorders via mechanisms that remain unclear. Here, we show that the levels of the hepatokine transthyretin (TTR) in circulation are elevated in insulin-resistant individuals including high-fat diet (HFD)-induced obese mice, db/db mice, and patients with metabolic syndrome. Liver Ttr mRNA and circulating TTR levels were reduced in mice by treadmill training, as was the TTR levels in quadriceps femoris muscle; however, AMP-activated protein kinase (AMPK) signaling activity was enhanced. Transgenic overexpression of TTR or injection of purified TTR triggered insulin resistance in mice fed on regular chow (RC). Furthermore, TTR overexpression reduced the beneficial effects of exercise on insulin sensitivity in HFD-fed mice. TTR was internalized by muscle cells via the membrane receptor Grp78 and the internalization into the quadriceps femoris was reduced by treadmill training. The TTR/Grp78 combination in C2C12 cells was increased, whereas the AMPK activity of C2C12 cells was decreased as the TTR concentration rose. In addition, Grp78 silencing prevented the TTR internalization and reversed its inhibitory effect on AMPK activity in C2C12 cells. Our study suggests that elevated circulating TTR may contribute to insulin resistance and counteract the exercise-induced insulin sensitivity improvement; the TTR suppression might be an adaptive response to exercise through enhancing AMPK activity in skeletal muscles.NEW & NOTEWORTHY Exercise improves obesity-induced insulin resistance via mechanisms that remain unclear. The novel findings of the study are that circulating TTR (a hepatokine) level is decreased by exercise, and the elevated circulating TTR, as was the elevated transthyretin internalization mediated by Grp78, counteracts the exercise-induced insulin sensitivity by downregulating AMPK activity in skeletal muscle of obese mice. These data suggest that TTR suppression might be an adaptive response to exercise through the crosstalk between liver and muscle.


Assuntos
Resistência à Insulina/genética , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Pré-Albumina/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica , Gorduras na Dieta/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Músculo Esquelético/efeitos dos fármacos , Obesidade/genética , Condicionamento Físico Animal/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
14.
Food Chem ; 354: 129570, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-33761340

RESUMO

While tissue fatty acid compositions reflect that of the dietary lipid source, little information is available on how dietary oils modify lipid class and molecular species profiles in hepatopancreas of crustacean. Herein, an 8-week nutritional trial and untargeted lipidomic analysis were used to investigate the impacts of dietary n-3 PUFA lipid sources including fish oil, krill oil and linseed oil on the lipidomic characteristics of hepatopancreas of swimming crab (Portunus trituberculatus). Dietary krill oil significantly increased distribution of 20:5n-3 and 22:6n-3 at sn-2 in phosphatidylcholine and phosphatidylethanolamine compared to fish oil. Fish oil intake promoted the deposition of 20:5n-3 and 22:6n-3 at sn-1,2,3 in triglyceride compared to linseed oil, which significantly increased the specific accumulation of 18:3n-3 at sn-1,3 in triglyceride and sn-2 in phosphatidylcholine and phosphatidylethanolamine. The study revealed metabolic responses to different dietary n-3 PUFA in swimming crab, which provided novel insight into the lipid nutrition of crustacean.


Assuntos
Braquiúros/efeitos dos fármacos , Braquiúros/metabolismo , Gorduras na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Lipidômica , Natação , Animais , Dieta , Estado Nutricional/efeitos dos fármacos
15.
Am J Physiol Endocrinol Metab ; 320(4): E786-E796, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33586490

RESUMO

We investigated the expression levels of nephroblastoma overexpressed [NOV or CCN3 (cellular communication network factor 3)] in the serum and placenta of pregnant women and of pregnant mice fed a high-fat diet (HFD), and its effect on placental glucose transporter 3 (GLUT3) expression, to examine its role in gestational diabetes mellitus (GDM). NOV/CCN3 expression was increased in the mouse serum during pregnancy. At gestational day 18, NOV/CCN3 protein expression was increased in the serum and placenta of the HFD mice compared with that of mice fed a normal diet. Compared with non-GDM patients, the patients with GDM had significantly increased serum NOV/CCN3 protein expression and placental NOV/CCN3 mRNA expression. Therefore, we hypothesized that NOV/CCN3 signaling may be involved in the pathogenesis of GDM. We administered NOV/CCN3 recombinant protein via intraperitoneal injections to pregnant mice fed HFD or normal diet. NOV/CCN3 overexpression led to glucose intolerance. Combined with the HFD, NOV/CCN3 exacerbated glucose intolerance and caused insulin resistance. NOV/CCN3 upregulates GLUT3 expression and affects the mammalian target of rapamycin (mTOR) pathway in the GDM environment in vivo and in vitro. In summary, our results demonstrate, for the first time, the molecular mechanism of NOV/CCN3 signaling in maternal metabolism to regulate glucose balance during pregnancy. NOV/CCN3 may be a potential target for detecting and treating GDM.NEW & NOTEWORTHY NOV/CCN3 regulates glucose homeostasis in mice during pregnancy. NOV/CCN3 upregulates GLUT3 expression and affects the mTOR pathway in the GDM environment in vivo and in vitro.


Assuntos
Dieta Hiperlipídica , Transportador de Glucose Tipo 3/genética , Proteína Sobre-Expressa em Nefroblastoma/genética , Serina-Treonina Quinases TOR/metabolismo , Animais , Células Cultivadas , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Gorduras na Dieta/farmacologia , Feminino , Glucose/metabolismo , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Humanos , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Gravidez , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
16.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478060

RESUMO

Controlling the differentiation potential of adipose-derived stem cells (ADSCs) is attracting attention as a new strategy for the prevention and treatment of obesity. Here, we aimed to observe the effect of exercise training (TR) and high-fat diet (HFD) on the metabolic profiles of ADSCs-derived adipocytes. The rats were divided into four groups: normal diet (ND)-fed control (ND-SED), ND-fed TR (ND-TR), HFD-fed control (HFD-SED), and HFD-fed TR (HFD-TR). After 9 weeks of intervention, ADSCs of epididymal and inguinal adipose tissues were differentiated into adipocytes. In the metabolome analysis of adipocytes after isoproterenol stimulation, 116 metabolites were detected. The principal component analysis demonstrated that ADSCs-derived adipocytes segregated into four clusters in each fat pad. Amino acid accumulation was greater in epididymal ADSCs-derived adipocytes of ND-TR and HFD-TR, but lower in inguinal ADSCs-derived adipocytes of ND-TR, than in the respective controls. HFD accumulated several metabolites including amino acids in inguinal ADSCs-derived adipocytes and more other metabolites in epididymal ones. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that TR mainly affected the pathways related to amino acid metabolism, except in inguinal ADSCs-derived adipocytes of HFD-TR rats. These findings provide a new way to understand the mechanisms underlying possible changes in the differentiation of ADSCs due to TR or HFD.


Assuntos
Adipócitos/metabolismo , Dieta Hiperlipídica , Metaboloma , Condicionamento Físico Animal/fisiologia , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Adipogenia/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Gorduras na Dieta/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Metaboloma/efeitos dos fármacos , Cultura Primária de Células , Ratos , Gordura Subcutânea/citologia , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismo
17.
J Nutr Biochem ; 90: 108570, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33429036

RESUMO

Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy. At the end of the intervention period, colon samples were harvested, mucosa fraction isolated, and RNA sequenced. Gene differential expression and enrichment analyses indicated that dietary patterns and atorvastatin therapy differentially altered gene expression, with diet-statin interactions. Atorvastatin had a more profound effect on differential gene expression than diet. In pigs not receiving atorvastatin, the WD upregulated "LXR/RXR Activation" pathway compared to pigs fed the HHD. Enrichment analysis indicated that atorvastatin therapy lowered inflammatory status in the HHD-fed pigs, whereas it induced a colitis-like gene expression phenotype in the WD-fed pigs. No significant association was identified between gene expression phenotypes and severity of atherosclerotic lesions in the left anterior descending-left circumflex bifurcation artery. These data suggested diet quality modulated the response to atorvastatin therapy in colonic mucosa, and these effects were unrelated to atherosclerotic lesion development.


Assuntos
Atorvastatina/farmacologia , Colo/metabolismo , Doença da Artéria Coronariana/tratamento farmacológico , Dieta/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Transcriptoma/efeitos dos fármacos , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Colesterol na Dieta/farmacologia , Colo/efeitos dos fármacos , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Dieta Saudável/métodos , Dieta Hiperlipídica/métodos , Dieta Ocidental , Gorduras na Dieta/farmacologia , Comportamento Alimentar , Feminino , Expressão Gênica , Humanos , Masculino , Suínos
18.
Am J Physiol Endocrinol Metab ; 320(3): E438-E452, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33427054

RESUMO

Obesity is a prevailing problem across the globe. Women who are obese have difficulty initiating and sustaining lactation. However, the impact of genetics and diet on breastfeeding outcomes is understudied. Here we explore the effect of diet and genotype on lactation. We utilized the low-density lipoprotein receptor (Ldlr-KO) transgenic mouse model as an obesity and hypercholesterolemia model. Additionally, we used the tryptophan hydroxylase 1 (Tph1-KO) mouse, recently identified as a potential anti-obesogenic model, to investigate if addition of Tph1-KO could ameliorate negative effects of obesity in Ldlr-KO mice. We created a novel transgenic mouse line by combining the Ldlr and Tph1 [double knockout (DKO)] mice to study the interaction between the two genotypes. Female mice were fed a low-fat diet (LFD; 10% fat) or high-fat diet (HFD; 60% fat) from 3 wk of age through early [lactation day 3 (L3)] or peak lactation [lactation day 11 (L11)]. After 4 wk of consuming either LFD or HFD, female mice were bred. On L2 and L10, dams were milked to investigate the effect of diet and genotype on milk composition. Dams were euthanized on L3 or L11. There was no impact of diet or genotype on milk protein or triglycerides (TGs) on L2; however, by L10, Ldlr-KO and DKO dams had increased TG levels in milk. RNA-sequencing of L11 mammary glands demonstrated Ldlr-KO dams fed HFD displayed enrichment of genes involved in immune system pathways. Interestingly, the DKO may alter vesicle budding and biogenesis during lactation. We also quantified macrophages by immunostaining for F4/80+ cells at L3 and L11. Diet played a significant role on L3 (P = 0.013), but genotype played a role at L11 (P < 0.0001) on numbers of F4/80+ cells. Thus the impact of diet and genotype on lactation differs depending on stage of lactation, illustrating complexities of understanding the intersection of these parameters.NEW & NOTEWORTHY We have created a novel mouse model that is focused on understanding the intersection of diet and genotype on mammary gland function during lactation.


Assuntos
Dieta Hiperlipídica , Lactação , Glândulas Mamárias Animais/metabolismo , Receptores de LDL/genética , Triptofano Hidroxilase/genética , Animais , Gorduras na Dieta/farmacologia , Feminino , Interação Gene-Ambiente , Genótipo , Lactação/efeitos dos fármacos , Lactação/genética , Glândulas Mamárias Animais/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna/genética , Camundongos , Camundongos Knockout , Camundongos Obesos , Obesidade/genética , Obesidade/metabolismo
19.
Am J Physiol Endocrinol Metab ; 320(3): E566-E580, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33427045

RESUMO

Sex as a biological variable has been the focus of increasing interest. Relatively few studies have focused, however, on differences in peripheral taste function between males and females. Nonetheless, there are reports of sex-dependent differences in chemosensitivity in the gustatory system. The involvement of endogenous changes in ovarian hormones has been suggested to account for taste discrepancies. Additionally, whether sex differences exist in taste receptor expression, activation, and subsequent signaling pathways that may contribute to different taste responsiveness is not well understood. In this study, we show the presence of both the nuclear and plasma membrane forms of estrogen receptor (ER) mRNA and protein in mouse taste cells. Furthermore, we provide evidence that estrogen increases taste cell activation during the application of fatty acids, the chemical cue for fat taste, in taste receptor cells. We found that genes important for the transduction pathway of fatty acids vary between males and females and that these differences also exist across the various taste papillae. In vivo support for the effect of estrogens in taste cells was provided by comparing the fatty acid responsiveness in male, intact female, and ovariectomized (OVX) female mice with and without hormone replacement. In general, females detected fatty acids at lower concentrations, and the presence of circulating estrogens increased this apparent fat taste sensitivity. Taken together, these data indicate that increased circulating estrogens in the taste system may play a significant role in physiology and chemosensory cellular activation and, in turn, may alter taste-driven behavior.NEW & NOTEWORTHY Using molecular, cellular, and behavioral analyses, this study shows that sex differences occur in fat taste in a mouse model. Female mice are more responsive to fatty acids, leading to an overall decrease in intake and fatty acid preference. These differences are linked to sex hormones, as estradiol enhances taste cell responsiveness to fatty acids during periods of low circulating estrogen following ovariectomy and in males. Estradiol is ineffective in altering fatty acid signaling during a high-estrogen period and in ovariectomized mice on hormone replacement. Thus, taste receptor cells are a direct target for actions of estrogen, and there are multiple receptors with differing patterns of expression in taste cells.


Assuntos
Gorduras na Dieta/farmacologia , Estradiol/sangue , Papilas Gustativas/efeitos dos fármacos , Paladar/fisiologia , Animais , Células Cultivadas , Gorduras na Dieta/metabolismo , Ciclo Estral/genética , Ciclo Estral/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ovariectomia , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Caracteres Sexuais , Paladar/efeitos dos fármacos , Papilas Gustativas/metabolismo , Percepção Gustatória/fisiologia
20.
J Nutr ; 151(1): 223-234, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33296473

RESUMO

BACKGROUND: Restaurant oil in poultry diets increases energy content, reduces production costs, and promotes sustainability within the food supply chain. However, variable oil composition and heating temperatures among restaurant oil sources can impact broiler chicken health due to heat-induced lipid modifications. OBJECTIVES: A 21-d experiment was conducted to evaluate ileal morphology, liver cytokine gene expression, and ileal immune cell populations in broilers fed control or peroxidized lipids with varying chain and saturation characteristics. METHODS: Day-old broilers were housed in battery cages (5 birds per cage) and fed diets containing 5% control or peroxidized oils. Eight diets were randomly assigned in a 4 × 2 factorial arrangement consisting of oil source (palm, soybean, flaxseed, or fish) and peroxidation status (control or peroxidized). At day 21, samples were collected for ileal histomorphology [villus height (VH), crypt depth (CrD), and the VH:CrD ratio], and liver cytokine expression (qPCR). Ileum cytokine expression and T-cell markers were analyzed by RNAscope in situ hybridization (ISH). Data were analyzed as a mixed model (SAS 9.4) with fixed effects of lipid source, peroxidation, and lipid × peroxidation interaction. RESULTS: CD3+ T-cells in the ileum decreased 16.2% due to peroxidation (P = 0.001) with 30.3% reductions observed in birds fed peroxidized flaxseed oil (P = 0.01). Peroxidation increased IL6+ and IL1B+ cells by 62.0% and 40.3%, respectively (P = 0.01). Soybean oil increased IFNG+ cells by 55.1% compared with palm oil, regardless of peroxidation status (P = 0.007). Lipid source and peroxidation did not alter ileal histomorphology or liver cytokine expression. CONCLUSIONS: Lipid peroxidation increased ileal IL1B and IL6 in broiler chickens, whereas soybean oil diets increased IFNG. Generally, peroxidation decreased overall CD3+ T-cell populations, suggesting impaired T-cell presence or recruitment. These results identify potential immunomodulatory lipid profiles in restaurant oil while supporting RNAscope-ISH as a method to describe avian tissue-level immune responses.


Assuntos
Ração Animal , Galinhas , Gorduras na Dieta/análise , Gorduras na Dieta/farmacologia , Imunidade Celular/efeitos dos fármacos , Animais , Citocinas/genética , Citocinas/metabolismo , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Íleo/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
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