Oral supplementation with resveratrol improves hormonal profile and increases expression of genes associated with thermogenesis in oophorectomy mice.

Menopause causes important bodily and metabolic changes, which favor the increased occurrence of cardiovascular diseases, obesity, diabetes, and osteoporosis. Resveratrol exerts proven effects on body metabolism, improving glucose and lipid homeostasis and reducing inflammation and oxidative stress in various organs and tissues. Accordingly, this study evaluates the effects of resveratrol supplementation on the expression of markers associated with thermogenesis in brown adipose tissue, and on the body, metabolic and hormonal parameters of female mice submitted to bilateral oophorectomy. Eighteen female mice were randomized into three groups: G1: control (CONTROL), G2: oophorectomy (OOF), and G3: oophorectomy + resveratrol (OOF + RSV); the animals were kept under treatment for twelve weeks, being fed a standard diet and treated with resveratrol via gavage. Body, biochemical, hormonal, and histological parameters were measured; in addition to the expression of markers associated with thermogenesis in brown adipose tissue. The results showed that animals supplemented with resveratrol showed reduced body weight and visceral adiposity, in addition to glucose, total cholesterol, and triglyceride levels; decreased serum FSH levels and increased estrogen levels were observed compared to the OOF group and mRNA expression of PRDM16, UCP1, and SIRT3 in brown adipose tissue. The findings of this study suggest the important role of resveratrol in terms of improving body, metabolic, and hormonal parameters, as well as modulating markers associated with thermogenesis in brown adipose tissue of female mice submitted to oophorectomy.

Curcumin improves metabolic response and increases expression of thermogenesis-associated markers in adipose tissue of male offspring from obese dams.

Maternal obesity and dietary style in the pregnancy-lactation period may result in long-term effects on the metabolic health of the offspring, thus increasing the risk of diseases, such as obesity, diabetes, and cardiovascular diseases. Curcumin is a natural polyphenolic compound that has beneficial properties on metabolism. Accordingly, this study is intended to evaluate the effects of curcumin supplementation in pregnant and lactating female mice on the anthropometric, metabolic and molecular parameters of the offspring fed a hyperglycemic diet. The study was conducted with 24 male mice randomized into three groups: i) control group (SD) originating from dams fed a standard diet; ii) hyperglycemic group (HGD) originating from dams fed a hyperglycemic diet; iii) curcumin group (CUR) originating from dams fed a hyperglycemic diet and supplemented with curcumin in the pregnancy-lactation period. All offspring groups were fed a hyperglycemic diet for 12 weeks. Anthropometricand biochemical parameters were measured, as well as the expression of thermogenesis-associated markers in the interscapular brown and inguinal white adipose tissues. The results showed less weight gain in the CUR group, with a concomitant reduction in food consumption compared to the HGD group. Biochemical parameters indicated lower levels of total cholesterol, glucose, and insulin for the CUR group, in addition to improved glucose tolerance and insulin sensitivity. The molecular evaluation indicated increased mRNA expression levels of UCP1 and PRDM16 in the brown and white adipose tissues. It is concluded that curcumin supplementation in the pregnancy-lactation period in dams with diet-induced obesity may lead to improvements in the offspring's metabolic phenotype, even if they are submitted to an obesogenic environment, possibly via thermogenesis activation.

Comparative study of dietary fat: lard and sugar as a better obesity and metabolic syndrome mice model.

BACKGROUND: Diet macronutrient heterogeneity hinders animal studies' data extrapolation from metabolic disorders to human diseases. OBJECTIVE: The present study aimed to evaluate different fat-diet compositions' effect on inducing lipid/glucose metabolism alterations in mice. METHODS: Swiss male mice were fed for 12 weeks with five different diets: Standard Diet (ST), American Institute of Nutrition 93 for growth (AIN93G) high-butter/high-sugar (HBHS), high-lard/high-sugar (HLHS), and high-oil/high-sugar diet (soybean oil) (HOHS). Several parameters, such as serum biochemistry, histology, and liver mRNA expression, were accessed. RESULTS: The main findings revealed that the HLHS diet dramatically altered liver metabolism inducing hepatic steatosis and increased total cholesterol, triglycerides, VLDL, increasing liver CCAAT/enhancer binding protein (CEBP-α), Acetyl-CoA carboxylase (ACC) and Catalase (CAT) mRNA expression. Moreover, the HLHS diet increased glucose intolerance and reduced insulin sensitivity. CONCLUSIONS: High-fat/high-sugar diets are efficient to induce obesity and metabolic syndrome-associated alterations, and diets enriched with lard and sugar showed more effective results.

Association Between Triglycerides, High-Density Lipoprotein Cholesterol, and Their Ratio With the Pulse Wave Velocity in Adults From the ELSA-Brasil Study.

Atherogenic dyslipidemia is a risk factor for cardiovascular diseases. The present study aimed to evaluate the association between triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and the triglycerides to high-density lipoprotein (TG/HDL-C) ratio with carotid-femoral pulse wave velocity (cf-PWV), a marker of vascular stiffness. Anthropometric, biochemical, and clinical data from 13,732 adults were used to assess this association. Individuals within the third TG/HDL-C tertile presented worse anthropometric, biochemical, and clinical profiles as compared with the participants in the lower TG/HDL-C tertile. There was a linear association between TG, HDL-C, and TG/HDL-C ratio and cf-PWV in both men and women (stronger in women). After adjustment for confounders, lower levels of HDL-C were associated with increased cf-PWV in men (9.63 ± .02 m/s) and women (8.90 ± .03 m/s). However, TG was not significantly associated with cf-PWV after adjustment, regardless of sex. An increased TG/HDL-C ratio is associated with higher cf-PWV only in women (9.01 ± .03 m/s), but after adjustment for HDL-C levels, the association was non-significant (8.99 ± .03 m/s). These results highlight the stronger association of HDL-C with arterial stiffness, and that the association of TG/HDL-C with cf-PWV is dependent on HDL-C.

Reference values for the triglyceride to high-density lipoprotein ratio and its association with cardiometabolic diseases in a mixed adult population: The ELSA-Brasil study.

BACKGROUND: Among several lipid ratios available, the triglyceride/HDL-cholesterol (TG/HDL-C) may detect individuals at risk of cardiometabolic diseases. However, its reference values for different ethnicities are not well established. OBJECTIVE: To define sex- and ethnicity-specific reference values for TG/HDL-C ratio in a large sample of healthy multiethnic adults and test its association with cardiometabolic conditions. METHODS: An apparently healthy sample (n = 2,472), aged 35-74, free of major cardiovascular risk factors, was used to generate the reference values for the TG/HDL-C. Exclusion criteria were diabetes, elevated blood pressure, obesity, hypercholesterolemia, severe hypertriglyceridemia, and smoking history. Cut-offs based on the reference values were tested in the whole ELSA Brasil study (n = 13,245), stratified by sex and ethnicity, to identify cardiometabolic conditions. RESULTS: TG/HDL-C ratio was higher in men than women, and did not change significantly with age, regardless of sex and ethnicity. Also, black individuals showed lower levels of TG/HDL-C as compared to other ethnic groups. ROC curve showed that the cut-off based on the 75th percentile displayed better sensitivities and specificities for men and women, regardless of ethnicity. Also, the sex- and ethnicity-specific cut-offs based on the 75th percentile were significantly associated with all tested cardiometabolic conditions (hypertension, diabetes, obesity, metabolic syndrome, and insulin resistance). Also, we observed that the use of a single sex-specific cut-off (men: 2.6; women: 1.7) could be used for the different ethnicities with good reliability. CONCLUSION: The defined TG/HDL-C cut-offs (men: 2.6; women: 1.7) are reliable and showed good clinical applicability to detect cardiometabolic conditions in a multiethnic population.

Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Enalapril improves obesity associated liver injury ameliorating systemic metabolic markers by modulating Angiotensin Converting Enzymes ACE/ACE2 expression in high-fat feed mice.

Obesity is a chronic disease caused multiple associated factors that results in excessive body fat accumulation. The Renin-Angiotensin System (RAS) unbalance is now recognized as a key factor on regulating body energy and metabolism. AIM: The aim of the present study was to evaluate the Enalapril (ACE inhibitor) effects on the metabolic function and hepatic steatosis of obese mice evaluating Angiotensin Converting Enzymes (ACEs) expression. METHODS: The experiment was performed using 32 male Swiss mice (8 weeks old) equally and randomly divided into 4 groups (n = 8): standard diet (ST), standard diet plus Enalapril (ST + ENAL), hyperlipidic diet (HF) and hyperlipidic diet plus Enalapril (HF + ENAL). Weekly measurements of animal weight and feed consumption were performed. At the end of treatment period a glucose tolerance test (GTT) and insulin sensitivity test (IST) were performed. Ultrasonography was used to evaluate hepatic and epididymal fat pad. Liver samples were submitted to HE histology and gene expression analyses were performed using Real-Time PCR. RESULTS: The main results showed a decrease in body weight after treatment with Enalapril, as well as a reduced size of epididymal fat pad (EFP). Hepatic echogenicity and steatosis measurement were lower in the obese groups treated with Enalapril also modulating ACE2/ACE expressions. CONCLUSIONS: Enalapril use improved metabolism reducing hepatic steatosis, decreasing ACE expression and increasing ACE2 expression.

Adherence to medication, physical activity and diet among older people living with diabetes mellitus: Correlation between cognitive function and health literacy.

BACKGROUND: Diabetes mellitus (DM) is a public health problem, which requires enhanced self-care in order to avoid complications. However, cognitive impairment can reduce these abilities and may affect health literacy (HL) of patients in terms to understand and apply information. Therefore, this study evaluated the correlation between cognitive condition and HL related to medication adherence, physical activity and nutritional status among people living with DM. METHODS: A cross-sectional study was carried out among elderly people (≥ 60 years old) with DM. The cognitive condition was evaluated using the Mini-Mental State Examination (MMSE) and the HL using the following questionnaires: Literacy Assessment for Diabetes (LAD-60), Nutritional Literacy among People with Diabetes (NLD), Health Literacy on the Practice of Physical Activities among Diabetics (HLPPA - D), and Health Literacy regarding Drug Adherence among Diabetics (HLDA-D). Sociodemographic and biochemical profile was also evaluated. Spearman correlation was used (p < 0.05). RESULTS: 187 individuals with DM were included. Regarding laboratory analyses, insulin dosage had a mean value of 12.3 microUI/mL (SD: ±15.7), mean blood glucose was 148.1 mg/dl (SD: ±59.7) and mean HbA1c was 7.54 % (SD: ±1.8). In the correlation analysis, higher age and lower income were weakly correlated with lower cognitive level. No correlation was identified for biochemical variables and cognitive condition. A positive and weak correlation between cognition and HL was observed in the studied population. CONCLUSIONS: In older people living with DM the cognitive condition is correlated to specific topics of HL (nutritional status, physical activity and medication adherence).

High fructose intake and the route towards cardiometabolic diseases.

It is known that dietary habits have a strong influence on body metabolism. In the last decades, the dietary habits have changed worldwide, and the consumption of fructose, especially in sugar-sweetened beverages, increased significantly. In this perspective, the present review aimed to summarize the effects of fructose on different cardiometabolic conditions. Clinical, experimental, and epidemiological studies evidenced that fructose can exert several deleterious effects when its consumption is above the recommended amounts. The increased fructose consumption decreases satiety, favoring a positive energy balance, increases adipogenesis, leading to visceral fat accumulation, induces ectopic fat accumulation, especially in the skeletal muscle and liver, leading to insulin resistance, inflammation, and lipid metabolism impairment, increases arterial blood pressure and causes vascular damage. Therefore, increased fructose consumption is linked to the development of alarming cardiometabolic conditions, such as obesity, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular diseases, through several different mechanisms. Further clinical and experimental studies are still necessary to elucidate additional signaling pathways and mechanisms by which fructose is involved in all the mentioned cardiometabolic disorders. Also, the reported findings raise the need for the creation of public health policies aimed to prevent diet-associated cardiometabolic disorders, thus improving the population quality of life.

Oral gallic acid improves metabolic profile by modulating SIRT1 expression in obese mice brown adipose tissue: A molecular and bioinformatic approach.

AIMS: The aim of the presente study was to examine the effects of oral gallic acid (GA) administration on the brown adipose tissue of obese mice fed with high-fat diet. New mechanisms and interactions pathways in thermogenesis were accessed through bioinformatics analyses. MAIN METHODS: Swiss male mice were divided into four groups and fed during 60 days with: standard diet, standard diet combined with gallic acid, high-fat diet and high-fat diet combined with gallic acid. Body weight, food intake, and blood parameters (glucose tolerance test, total-cholesterol, high-density low-c, triglyceride and glucose levels) were evaluated. Brown and subcutaneous white adipose tissue histological analysis were performed. SIRT1 and PGC1-α mRNA expression in the brown adipose tissue were assessed. KEY FINDINGS: Our main findings showed that the gallic acid improved glucose tolerance and metabolic parameters. These results were accompanied by bioinformatics analyses that evidenced SIRT1 as main target in the thermogenesis process, confirmed as increased SIRT1 mRNA expression was evidenced in the brown adipose tissue. SIGNIFICANCE: Together, the data suggest that the gallic acid effect in brown adipose tissue may improve body metabolism, glucose homeostasis and increase thermogenesis.

Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population.

OBJECTIVE: The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. SUBJECTS AND METHODS: The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. RESULTS: The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). CONCLUSIONS: We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population

ABSTRACT Objective The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. Subjects and methods The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. Results The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). Conclusions We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

Angiotensin-(1-7), Adipokines and Inflammation.

Nowadays the adipose tissue is recognized as one of the most critical endocrine organs releasing many adipokines that regulate metabolism, inflammation and body homeostasis. There are several described adipokines, including the renin-angiotensin system (RAS) components that are especially activated in some diseases with increased production of angiotensin II and several pro-inflammatory hormones. On the other hand, RAS also expresses angiotensin-(1-7), which is now recognized as the main peptide on counteracting Ang II effects. New studies have shown that increased activation of ACE2/Ang-(1-7)/MasR arm can revert and prevent local and systemic dysfunctions improving lipid profile and insulin resistance by modulating insulin actions, and reducing inflammation. In this context, the present review shows the interaction and relevance of Ang-(1-7) effects on regulating adipokines, and as one adipokine itself, modulating body homeostasis, with emphasis on its anti-inflammatory properties, especially in the context of metabolic disorders with focus on obesity and type 2 diabetes mellitus pandemic.

Effect of resveratrol on expression of genes involved thermogenesis in mice and humans.

The present study aimed to evaluate the effects of resveratrol on FNDC5 and thermogenesis markers expression in the adipose tissue of mice and humans. Thirty-two male mice were randomly divided into four groups (n = 8) and fed with: Standard Diet; Standard Diet + Resveratrol (400 mg/kg); High-fat Diet; High-fat Diet + Resveratrol for eight weeks. Twenty male and female volunteers, aged 30-55 years, BMI ≥ 30 kg/m² were divided into two groups and treated for four weeks with 500 mg trans-resveratrol or placebo, adipose tissue biopsies were taken. Analysis of body weight, food intake, glycemic and lipid profiles, mRNA expression from tissues and primary culture of adipocytes were performed. The main results show that resveratrol improves the glycaemic and lipid profiles along with an increase in the levels of UCP1, PRDM16, PGC1α, and SIRT1. The increase in FNDC5 expression was observed in the mouse and human subcutaneous adipose tissue. The SIRT1 antagonist in adipocyte primary culture resulted in decreased FNDC5 expression. Our data suggest that improved metabolism produced by oral administration of resveratrol is, at least in part, associated with increased thermogenesis followed by high expression of UCP1, PRDM16, PGC1α and that increased FNDC5 expression in the subcutaneous adipose tissue from mice and human might be modulated by SIRT1.

Sclareol-loaded lipid nanoparticles improved metabolic profile in obese mice.

Sclareol is a bioactive hydrophobic diterpene in the essential oil isolated from Salvia sclarea (Fam. Lamiaceae). Sclareol has been widely studied due to its anti-inflammatory and antioxidant effects. AIMS: The present study aimed to evaluate the effects of Sclareol in different formulations (solid lipid nanoparticle and free) on the metabolic profile of obese mice. MAIN METHODS: Swiss male mice were randomly divided into two groups: standard diet (STD) and high-fat diet (HFD). After obesity induction, each group was divided into three treatment groups: free Sclareol (Sc), Sclareol-loaded lipid nanoparticle (L-Sc) and blank lipid nanoparticle (L). Treatments were performed every day during 30 days. KEY FINDINGS: L-Sc improves obese mice metabolic profile by decreasing adiposity, ameliorating insulin sensitivity, glucose tolerance and increasing the HDL plasma levels. In addition, L-Sc decreased the expression of NF-KB, MCP-1 and SERBP-1. SIGNIFICANCE: The use of sclareol together with lipid nanocarriers may be promising for the treatment of metabolic disorders by reducing adipose tissue.

Nuclear sirtuins and inflammatory signaling pathways.

The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms. Nuclear sirtuins (SIRT 1, 2, 6 and 7) in particular may play an important role in the regulation of inflammatory responses. In the present review, we assessed the roles of nuclear sirtuins in inflammatory reactions: SIRT1 has been shown to suppress NF-κb activity, the master regulator of cellular inflammatory response, decrease COX-2 and iNOS production, and increase antioxidant gene expression that suppressed inflammation. SIRT2 activity included the deacetylation of p65 subunit of NF-κß and RIP-1, while SIRT6 has been shown to interact with p65/RelA bound to the NF-κß promoter region and repress transcriptional activity. Furthermore, recent studies have shown that the absence of SIRT7 produced an increase in inflammation, illustrating that SIRT7 also functioned to decrease inflammation. Given their significant roles in the regulation of chronic inflammation, nuclear sirtuins represent potential therapeutic targets in the control of chronic inflammatory diseases.

Obesity and malnutrition similarly alter the renin-angiotensin system and inflammation in mice and human adipose.

The main goal of the present study was to evaluate the metabolic profile, inflammatory markers and the gene expression of the renin-angiotensin system (RAS) components in the visceral adipose tissue of eutrophic, obese and malnourished individuals and mice models of obesity and food restriction. Male Swiss mice were divided into eight groups and fed different levels of food restriction (20%, 40%, or 60%) using standard or high-fat diet. Metabolic profile and adipose tissues were assessed. The expression of AGT (Angiotensinogen), ACE (Angiotensin-converting enzyme), ACE2 (Angiotensin-converting enzyme 2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the mice epididymal adipose tissue and the human visceral adipose tissue was assessed. The main findings showed reduced body weight, improved metabolism, decreased adipose tissues weight and reduced adipocyte area in mice submitted to food restriction. Diminished expression of IL-6, TNF-α, AGT, AT1 and ACE was detected in the 20% and 40% food restriction animal groups, although they were increased in the 60% malnourished group. Increased expression of IL-6, TNF-α, AGT and ACE in obese and malnourished individuals was observed. Adipocytes size was increased in obese individuals and reduced in malnutrition. In conclusion, we found that food restriction of 20% and 40% improved the metabolic profile, ameliorated the inflammatory status and down-regulated the RAS in mice. Severe 60% food restriction (malnutrition), however, stimulated a proinflammatory state and increased AGT and ACE expression in the adipose tissue of mice. A similar profile was observed in the adipose tissue of obese and malnourished humans, supporting the critical role of inflammation and RAS as mediators of metabolic disorders.

Effects of Dietary Macronutrient Composition on FNDC5 and Irisin in Mice Skeletal Muscle.

BACKGROUND: Fibronectin type III domain containing 5 (FNDC5) and its protein product Irisin are therapeutic targets for obesity-associated disorders. Irisin plays an important role in energy regulation, inducing browning of white adipocytes, and improving obesity. We aimed to investigate the association between muscle Irisin expression and dietary quality. METHODS: Twenty-eight female mice were divided into four groups and fed the following experimental diets for 60 days: standard diet (SD), high-carbohydrate diet (HCD), high-fat diet (HFD), and high-protein diet (HPD). We evaluated body weight, food intake, serum total cholesterol, triacylglycerol, and glucose. We also performed glucose tolerance and insulin sensitivity tests. Expression of FNDC5 was evaluated by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) of soleus muscle. Western blot was used to assess Irisin protein expression. RESULTS: The major finding of the present study was that HFD and HCD were associated with a downregulation of FNDC5. In addition to these results, we noted a significant reduction in skeletal muscle Irisin level. HPD prevented reductions of both FNDC5 and Irisin levels, as well as increased brown adipose tissue, compared to the control group. CONCLUSIONS: In conclusion, we observed that the HPD type of diet can change both FNDC5 expression and Irisin levels. Thus, the HPD might be the most appropriate diet to achieve high amounts of Irisin, a target molecule for the treatment of obesity and its co-morbidities.