Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis.

BACKGROUND & AIMS: We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism. METHODS: We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells. RESULTS: Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes. CONCLUSIONS: Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.

Associations among diet costs, food prices and income: Elasticities of risk and protection food groups for cardiometabolic diseases in Sao Paulo, Brazil (2003-2015).

Background: Economic dimension comprises important determinants of food choices, particularly income and prices. Aim: Identification of the influence of food prices and diet costs on the consumption of food groups considered protection and risk factors for cardiometabolic diseases. Methods: Food groups classification follows the proposal of "What we eat in America?" from the National Health and Nutrition Examination Survey (NHANES), adapted to Latin America. Data on food consumption from the Health Survey of Sao Paulo (2003, 2008, and 2015), representative at population level, was used. Log-linear regressions were estimated for food groups, controlling for endogeneity through augmented regression-test Results: Results showed increase in prices per calorie of whole grains and red meat from 2003-2015 and a decrease in prices per calorie of fruits, vegetables, beans, legumes, oilseeds and fish/seafood. Food groups had price elasticities between -0.01 and -1.6, i.e., decrease in consumption associated with increase in prices. Results showed statistically significant effects of substitution and complementarity, particularly substitution between sweetened beverages and fruits (2003, ß = 0.606; 2008: ß = 0.683; 2015, ß = 0.848), complementarity between nuts and seeds and whole grains (2003, ß = -0.646; 2008, ß = -0.647; 2015,ß = -0.901), and vegetables and processed meat (2003, ß = -1.379; 2015, ß = -1.685). Conclusion: Findings of the study represent relevant evidence for design strategies towards the adoption of healthier diets, particularly through subsidies to protection food groups, promoting lower prices and higher diet quality. The evidence may be useful for policymakers and researchers in fields of nutrition and health in diverse countries worldwide, especially due to absence of robust evidence in literature.

Contribution of food groups to energy, grams and nutrients-to-limit: the Latin American Study of Nutrition and Health/Estudio Latino Americano de Nutrición y Salud (ELANS).

OBJECTIVE: To quantify the energy, nutrients-to-limit and total gram amount consumed and identify their top food sources consumed by Latin Americans. DESIGN: Data from the Latin American Study of Nutrition and Health (ELANS). SETTING: ELANS is a cross-sectional study representative of eight Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru and Venezuela. PARTICIPANTS: Two 24-h dietary recalls on non-consecutive days were used to estimate usual dietary intake of 9218 participants with ages between 15-65 years. 'What We Eat in America' food classification system developed by United States Department of Agriculture was adapted and used to classify all food items consumed by the ELANS population. Food sources of energy, added sugars, SFA, Na and total gram amount consumed were identified and ranked based on percentage of contribution to intake of total amount. RESULTS: Three-highest ranked food categories of total energy consumed were: rice (10·3%), yeast breads (6·9%), and turnovers and other grain-based items (6·8 %). Highest ranked food sources of total gram amount consumed were fruit drinks (9·6%), other 100% juice (9·3%) and rice (8·3%). Three highest ranked sources for added sugars were other 100% juice (24·1 %), fruit drinks (16·5%), and sugar and honey (12·4%). SFA ranked foods were turnovers and other grain-based (12·6 %), cheese (11·9%), and pizza (10·3%). Three top sources of Na were rice (13·9%), soups (9·1 %) and rice mixed dishes (7·3 %). CONCLUSION: Identification of top sources of energy and nutrients-to-limit among Latin Americans is critical for designing strategies to help them meet nutrient recommendations within energy needs.

Reemergence of human malaria in Atlantic Forest of Rio Grande do Sul, Brazil.

Unforeseen Plasmodium infections in the Atlantic Forest of Brazilian Extra-Amazonian region could jeopardise malaria elimination. A human malaria case was registered in Três Forquilhas, in the Atlantic Forest biome of Rio Grande do Sul, after a 45 years' time-lapsed without any malaria autochthonous notification in this southern Brazilian state. This finding represents the expansion of the malaria distribution areas in Brazil and the southernmost human malaria case record in South America in this decade. The coexistence of the bromeliad-breeding vector Anopheles (Kerteszia) cruzii and non-human primates in the Atlantic Forest regularly visited by the patient claimed for the zoonotic origin of this infection. The reemergence of Atlantic Forest human malaria in Rio Grande do Sul was also discussed.

Can fructose influence the development of obesity mediated through hypothalamic alterations?

Epidemiological data from the last decades point to an exponential growth in the number of obese people. Different behavioral factors, mainly associated with food consumption, appear to contribute significantly to its development. Concomitant with increased obesity rates, an increase in the consumption of fructose has been observed; therefore, fructose consumption has been implicated as an important obesogenic factor. However, changes in brain activity due to fructose consumption are possible, especially in relation to hypothalamic satiety mechanisms. In addition, the obese state may provide an environment of chronic inflammation and further contribute to the discontinuation of satiety mechanisms in the hypothalamus. We briefly review the intrinsic alterations to the increased adipose tissue, its connections with the hypothalamus in the control of energy signaling mechanisms and, consequently, the participation of fructose as a co-adjuvant or trigger. Presenting the current context with clinical trials involving human and animal studies, we seek to contribute to a better understanding of the role of fructose in the progression of obesity.

Social determinants, lifestyle and diet quality: a population-based study from the 2015 Health Survey of São Paulo, Brazil.

OBJECTIVE: To investigate the association among social determinants, lifestyle variables and diet quality in São Paulo, Brazil. DESIGN: Cross-sectional study, 2015 Health Survey of São Paulo (Inquérito de Saúde de São Paulo (2015 ISA-Capital)) with Focus on Nutrition Study (2015 ISA-Nutrition). SETTING: Population-based study, with a representative sample of adults living in São Paulo, Brazil. PARTICIPANTS: Adults (aged 20-59 years, n 643) and older adults (aged ≥60 years, n 545). RESULTS: We observed differences in the Brazilian Healthy Eating Index-Revised (BHEI-R) by education, income, occupation, sex and race. Whole grains (0·63 points, 12·6 % of the maximum score), sodium (2·50 points, 25·0 %) and solid fat, alcohol and added sugars (9·28 points, 46·4 %) components had the lowest BHEI-R scores. Factors positively associated with diet quality included the presence of one disease or more (e.g. diabetes mellitus, hypertension, cancer, hypercholesterolaemia: ß = 0·636, P < 0·001), income (middle income: ß = 0·478, P < 0·001; high income: ß = 0·966, P < 0·001) and occupation (other: ß = 1·418, P < 0·001). Energy (ß = -0·001, P < 0·001), alcohol consumption (ß = -0·207, P = 0·027), education level (middle education: ß = -0·975, P < 0·001; high education: ß = -1·376, P < 0·001), races other than white (ß = -0·366, P < 0·001) and being unemployed (ß = -0·369, P < 0·046) were negatively associated with diet quality. CONCLUSIONS: Groups affected by socio-economic inequalities need better diet quality. Governmental actions should be implemented to reduce the consumption of energy-dense and sodium-rich foods, facilitate access and information on healthy eating, and conduct nutritional education.

Omega-3 polyunsaturated fatty acids have beneficial effects on visceral fat in diet-induced obesity model.

This study evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oxidative stress and energy metabolism parameters in the visceral fat of a high-fat-diet induced obesity model. Energy intake, body mass, and visceral fat mass were also evaluated. Male Swiss mice received either a control diet (control group) or a high-fat diet (obese group) for 6 weeks. After this period, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + omega-3, and to these groups 400 mg·(kg body mass)-1·day-1 of fish oil (or saline) was administered orally, for 4 weeks. Energy intake and body mass were monitored throughout the experiment. In the 10th week, the animals were euthanized and the visceral fat (mesenteric) was removed. Treatment with omega-3 PUFAs did not affect energy intake or body mass, but it did reduced visceral fat mass. In visceral fat, omega-3 PUFAs reduced oxidative damage and alleviated changes to the antioxidant defense system and the Krebs cycle. The mitochondrial respiratory chain was neither altered by obesity nor by omega-3 PUFAs. In conclusion, omega-3 PUFAs have beneficial effects on the visceral fat of obese mice because they mitigate changes caused by the consumption of a high-fat diet.

The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity for repurposing a clinically used oncological drug for the experimental therapy of sepsis.

Poly(ADP-ribose) polymerase (PARP) is involved in the pathogenesis of cell dysfunction, inflammation and organ failure during septic shock. The goal of the current study was to investigate the efficacy and safety of the clinically approved PARP inhibitor olaparib in experimental models of oxidative stress in vitro and in sepsis in vivo. In mice subjected to cecal ligation and puncture (CLP) organ injury markers, circulating and splenic immune cell distributions, circulating mediators, DNA integrity and survival was measured. In U937 cells subjected to oxidative stress, cellular bioenergetics, viability and DNA integrity were measured. Olaparib was used to inhibit PARP. The results show that in adult male mice subjected to CLP, olaparib (1-10 mg/kg i.p.) improved multiorgan dysfunction. Olaparib treatment reduced the degree of bacterial CFUs. Olaparib attenuated the increases in the levels of several circulating mediators in the plasma. In the spleen, the number of CD4+ and CD8+ lymphocytes were reduced in response to CLP; this reduction was inhibited by olaparib treatment. Treg but not Th17 lymphocytes increased in response to CLP; these cell populations were reduced in sepsis when the animals received olaparib. The Th17/Treg ratio was lower in CLP-olaparib group than in the CLP control group. Analysis of miRNA expression identified a multitude of changes in spleen and circulating white blood cell miRNA levels after CLP; olaparib treatment selectively modulated these responses. Olaparib extended the survival rate of mice subjected to CLP. In contrast to males, in female mice olaparib did not have significant protective effects in CLP. In aged mice olaparib exerted beneficial effects that were less pronounced than the effects obtained in young adult males. In in vitro experiments in U937 cells subjected to oxidative stress, olaparib (1-100 µM) inhibited PARP activity, protected against the loss of cell viability, preserved NAD+ levels and improved cellular bioenergetics. In none of the in vivo or in vitro experiments did we observe any adverse effects of olaparib on nuclear or mitochondrial DNA integrity. In conclusion, olaparib improves organ function and extends survival in septic shock. Repurposing and eventual clinical introduction of this clinically approved PARP inhibitor may be warranted for the experimental therapy of septic shock.

Correction to: Frozen blood clots can be used for the diagnosis of distinct Plasmodium species in man and non-human primates from the Brazilian Atlantic Forest.

Following publication of the original article [1], it was flagged that one of the authors (Anielle de Pina Costa) is missing an affiliation in the article.

Diet-induced obesity causes hypothalamic neurochemistry alterations in Swiss mice.

The aim of this study was to assess inflammatory parameters, oxidative stress and energy metabolism in the hypothalamus of diet-induced obese mice. Male Swiss mice were divided into two study groups: control group and obese group. The animals in the control group were fed a diet with adequate amounts of macronutrients (normal-lipid diet), whereas the animals in the obese group were fed a high-fat diet to induce obesity. Obesity induction lasted 10 weeks, at the end of this period the disease model was validated in animals. The animals in the obese group had higher calorie consumption, higher body weight and higher weight of mesenteric fat compared to control group. Obesity showed an increase in levels of interleukin 1ß and decreased levels of interleukin 10 in the hypothalamus. Furthermore, increased lipid peroxidation and protein carbonylation, and decreased level of glutathione in the hypothalamus of obese animals. However, there was no statistically significant difference in the activity of antioxidant enzymes, superoxide dismutase and catalase. The obese group had lower activity of complex I, II and IV of the mitochondrial respiratory chain, as well as lower activity of creatine kinase in the hypothalamus as compared to the control group. Thus, the results from this study showed changes in inflammatory markers, and dysregulation of metabolic enzymes in the pathophysiology of obesity.

Frozen blood clots can be used for the diagnosis of distinct Plasmodium species in man and non-human primates from the Brazilian Atlantic Forest.

BACKGROUND: Zoonotic infections with epidemic potential, as non-human primate malaria and yellow fever (YF), can overlap geographically. Optimizing a small blood sample for diagnosis and surveillance is of great importance. Blood are routinely collected for YF diagnosis and blood clots usually discarded after serum obtention. Aiming to take sample advantage, the sensitivity of a PCR using extracted DNA from long-term frozen clots from human and non-human primates for detection of Plasmodium spp. in low parasitaemia conditions was assayed. RESULTS: Malaria diagnosis with DNA extracted from blood clots generated results in agreement with samples obtained with whole blood, including mixed Plasmodium vivax/simium and Plasmodium malariae/brasilianum infections. CONCLUSION: Blood clots from human and non-human primates may be an important and low cost source of DNA for malaria surveillance in the Atlantic Forest.

n-3 PUFA and obesity: from peripheral tissues to the central nervous system.

The current paradigms of prevention and treatment are unable to curb obesity rates, which indicates the need to explore alternative therapeutic approaches. Obesity leads to several damages to the body and is an important risk factor for a number of other chronic diseases. Furthermore, despite the first alterations in obesity being observed and reported in peripheral tissues, studies indicate that obesity can also cause brain damage. Obesity leads to a chronic low-grade inflammatory state, and the therapeutic manipulation of inflammation can be explored. In this context, the use of n-3 PUFA (especially in the form of fish oil, rich in EPA and DHA) may be an interesting strategy, as this substance is known by its anti-inflammatory effect and numerous benefits to the body, such as reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation, and has shown potential to help treat obesity. Thereby, the aim of this narrative review was to summarise the literature related to n-3 PUFA use in obesity treatment. First, the review provides a brief description of the obesity pathophysiology, including alterations that occur in peripheral tissues and at the central nervous system. In the sequence, we describe what are n-3 PUFA, their sources and their general effects. Finally, we explore the main topic linking obesity and n-3 PUFA. Animal and human studies were included and alterations on the whole organism were described (peripheral tissues and brain).

Determinants of inequalities in the quality of Brazilian diet: trends in 12-year population-based study (2003-2015).

BACKGROUND: Recent studies have explored the influence of socioeconomic inequalities on the diet quality. However, there is lack of evidence regarding the level of inequalities in dietary quality and its main contributing factors from population-based follow-up studies. The primary objective of this study was to investigate the level and the determinants of inequalities in diet quality in a representative sample of adolescents, adults and older adults resident in São Paulo, Brazil. METHODS: Data from the Health Survey of São Paulo (ISA-Capital) were analyzed for 2003 (n = 2398), 2008 (n = 1662) and 2015 (n = 1742) surveys. Information on food consumption was obtained through 24-h dietary recall, and diet quality was assessed based on the Revised Brazilian Healthy Eating Index (BHEI-R). The descriptive variables were compared using 95% confidence interval. The scores of BHEI-R and its components were compared across age groups and year. The association between socioeconomic inequalities and diet quality was based on the estimation of concentration index. RESULTS: We observed that the BHEI-R scores gradually improved over 12-years, with older adults showing the greatest improvement. The increase in overall population score was observed for total fruits, whole fruits, whole grains, oils and sodium. The main contributor to socioeconomic inequality in diet quality in 2003 was ethnic group, and in 2008 and 2015, it was per capita household income; age was a persistent factor of inequality in the population over the years. Concentration indices indicated that lower income individuals had higher BHEI-R scores in 2003; however, there was a shift in favor of higher income individuals in 2008 and 2015. CONCLUSIONS: Changes in the patterns of determination of inequalities according to age, ethnic group or income during the period analyzed show the existence of ongoing process of contribution of demographic and socioeconomic factors in the diet quality of individuals in a large urban center.

Single dose and repeated administrations of liraglutide alter energy metabolism in the brains of young and adult rats.

Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue that was recently approved to treat obesity in some countries. Considering that liraglutide effects on brain energy metabolism are little known, we evaluated the effects of liraglutide on the energy metabolism. Animals received a single or daily injection of saline or liraglutide during 7 days (25, 50, 100, or 300 µg/kg i.p.). Twenty-four hours after the single or last injection, the rats were euthanized and the hypothalamus, prefrontal cortex, cerebellum, hippocampus, striatum, and posterior cortex were isolated. Our results demonstrated that a single dose of liraglutide in young rats increased the activity of complexes and inhibited creatine kinase activity. Repeated administrations of liraglutide in young rats reduced the activity of complexes and activated creatine kinase activity. In adult rats, a single dose of liraglutide reduced the activity of complex I and creatine kinase and increased the activity of complexes II and IV. Repeated administrations of liraglutide in adult rats increased the activity of complexes I and IV and reduced the activity of complex II and creatine kinase. We concluded that liraglutide may interfere in energy metabolism, because analysis of different times of administrations, concentrations, and level of brain development leads to divergent results.

Effect of subchronic administration of agomelatine on brain energy metabolism and oxidative stress parameters in rats.

AIMS: The aim of this study was to investigate the effect of subchronic administration of agomelatine on energy metabolism, oxidative stress markers and antioxidant defense in the brains of rats. METHODS: The animals received daily intraperitoneal injections of agomelatine (10, 30 or 50 mg/kg) or saline for 14 days. The prefrontal cortex, cerebellum, hippocampus, striatum and posterior cortex were analyzed. RESULTS: The findings showed that complex I was activated in the prefrontal cortex, cerebellum and striatum and inhibited in the posterior cortex at the 10-mg/kg dose, and inhibited in all brain areas analyzed at the 30-mg/kg and 50-mg/kg doses. Complex II was activated in the posterior cortex at the 50-mg/kg dose. Complex IV was inhibited in the striatum and posterior cortex at the 10-mg/kg dose, inhibited in the striatum at the 30-mg/kg dose and activated in the hippocampus at the 50-mg/kg dose. Creatine kinase activity was inhibited in the striatum at the 10-mg/kg and 30-mg/kg doses. Lipid peroxidation and protein carbonylation levels were not changed after the administration of agomelatine. Superoxide dismutase activity was increased in the striatum at the 10-mg/kg dose, and catalase activity was inhibited in the cerebellum at the 10-mg/kg dose and increased in the posterior cortex at the 30-mg/kg dose. CONCLUSIONS: Our results are consistent with other studies showing that some antidepressants may influence brain energy metabolism and oxidative stress parameters and expand knowledge about the effects of agomelatine in biochemical parameters in the brains of rats.

Mitochondrial DNA control region diversity in a population from Espirito Santo state, Brazil.

Mitochondrial DNA (mtDNA) analysis has proved to be useful for forensic identification, especially in cases which nuclear DNA markers fail, as in degraded samples or in cases where the biological material has few traces or no nuclear DNA. Moreover, it can be applied in population genetics, inferring the origin of a population. In this work, the entire mtDNA control region of 97 individuals from the state of Espirito Santo, Brazil, was analyzed. We have found 94 different haplotypes yielding a high haplotype diversity of 0.9994 ± 0.0016. The probability of a random match calculated was 1.09. Haplogroup distribution analysis confirmed a highly admixed Latin American population: African lineages (43.3 %), European lineages (32.0 %), Native American lineages (23.7 %) and Asian lineages (1.0 %). We have concluded that this type of tool can be used both in forensic genetics to the study of different human populations, such as highly admixed populations, and in the study of migration's history and colonization of different states and countries of the world.

Effects of omega-3 on behavioral and biochemical parameters in rats submitted to chronic mild stress.

Major depression is a heterogeneous psychiatric disorder whose pathophysiology is not clearly established yet. Some studies have shown that oxidative stress and mitochondrial dysfunction are involved in the development of major depression. Since most depressed patients do not achieve complete remission of symptoms, new therapeutic alternatives are needed and omega-3 has been highlighted in this scenario. Therefore, we have investigated the effects of omega-3 on behavioral and biochemical parameters in rats submitted to chronic mild stress (CMS). Male Wistar rats were submitted to CMS for 40 days. After the CMS period, we administered a 500 mg/kg dose of omega-3 orally, once a day, for 7 days. The animals submitted to CMS presented anhedonia, had no significant weight gain, presented increased levels of lipid peroxidation and protein carbonylation, and inhibition of complex I and IV activities of the mitochondrial respiratory chain. The treatment with omega-3 did not reverse anhedonia; however, it reversed weight change, increased lipid peroxidation and protein carbonylation levels, and partially reversed the inhibition of mitochondrial respiratory chain complexes. The findings support studies that state that major depression is associated with mitochondrial dysfunction and oxidative stress, and that omega-3 supplementation could reverse some of these changes, probably due to its antioxidant properties.

ω-3 and major depression: a review.

BACKGROUND: The World Health Organization estimates that major depression affects about 350 million people all over the world and reports this disorder as the major contributor to the global burden of diseases. Despite the well-defined symptomatology, major depression is a heterogeneous psychiatric disorder whose pathophysiology is not clearly established. Although several treatments are available, most depressed patients do not achieve the complete remission of symptoms. Factors linked to the persistence of the disorder have been investigated, particularly those related to the way of life. Moreover, it has been suggested that nutritional aspects may influence its development. Among them, a diet rich in ω-3 has been associated with a reduced risk of major depression, although its deficiency is associated with depressive disorders. METHODS: This review provides a general view about evidences of the use of ω-3 in major depression cases. RESULTS: Several studies have demonstrated beneficial effects of ω-3 in the prevention and treatment of major depression. However, not all the results have shown significant statistical benefits. CONCLUSIONS: More studies are necessary to clarify detailed mechanisms of the antidepressant effects of ω-3 and may explain the source of contradictions in results published until the moment.

Are pvcrt-o and pvmdr1 Gene Mutations Associated with Plasmodium vivax Chloroquine-Resistant Parasites?

(1) Background: Malaria remains a significant global public health issue. Since parasites quickly became resistant to most of the available antimalarial drugs, treatment effectiveness must be constantly monitored. In Brazil, up to 10% of cases of vivax malaria resistant to chloroquine (CQ) have been registered. Unlike P. falciparum, there are no definitive molecular markers for the chemoresistance of P. vivax to CQ. This work aimed to investigate whether polymorphisms in the pvcrt-o and pvmdr1 genes could be used as markers for assessing its resistance to CQ. (2) Methods: A total of 130 samples from P. vivax malaria cases with no clinical and/or parasitological evidence of CQ resistance were studied through polymerase chain reaction for gene amplification followed by target DNA sequencing. (3) Results: In the pvcrt-o exons, the K10 insert was present in 14% of the isolates. Regarding pvmdr1, T958M and F1076L haplotypes showed frequencies of 95% and 3%, respectively, while the SNP Y976F was not detected. (4) Conclusions: Since K10-pvcrt-o and F1076L/T958M-pvmdr1 polymorphisms were detected in samples from patients who responded well to CQ treatment, it can be concluded that mutations in these genes do not seem to have a potential for association with the phenotype of CQ resistance.

Combination of Gold Nanoparticles with Carnitine Attenuates Brain Damage in an Obesity Animal Model.

Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.