Search Results (79)

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. Full article

Obesity is a major contributor to kidney injury, in part through circadian rhythms disruption and oxidative stress. Melatonin, a circadian clock regulator, has been proposed as a protective agent against metabolic and renal complications. We investigated the effects of chronic melatonin supplementation on kidney injury and circadian regulation in a rat obesity model. We hypothesized that melatonin administration ameliorates kidney injury induced by a high-calorie diet. Male Wistar rats were fed a normal or hypercaloric diet for six weeks, followed by seven weeks of vehicle or melatonin treatment (30 mg/kg/day in drinking water); biometric parameters and renal injury were assessed. Obese rats exhibited increased visceral adiposity, elevated resistin, renal hypertrophy, fibrosis, tubular degeneration, and glomerular injury, accompanied by higher KIM-1 levels. Melatonin attenuated renal fibrosis, reduced KIM-1, TGFβ, and TNFR1 levels, improved proximal tubule and glomerular damage, and lowered adipose TNF-α levels in the obese groups. In lean controls, melatonin increased nuclear BMAL1 levels, while in obese rats this effect was blunted; of note, BMAL1 accumulated in distal tubular cytoplasm in both melatonin-treated groups. These findings suggest that melatonin mitigates obesity-induced renal pathology through anti-fibrotic inflammation-related mechanisms, while also revealing a novel link between circadian disruption and kidney injury. Our results support melatonin as a therapeutic agent for obesity-related renal disease. Full article

A hypercaloric diet is associated with oxidative stress and the dysfunction of ATP-Binding Cassette transporter A1 (ABCA1), a key element in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. Nicotinamide (NAM) presents antioxidant properties, which may contribute to maintaining lipid metabolism. Therefore, we aimed to evaluate the effect of NAM on HDL-cholesterol (HDL-C) level, oxidative stress markers, and the gene expression and protein levels of ABCA1 in Sprague-Dawley rats fed a hypercaloric diet. Forty male rats were divided into five groups: one group received a standard diet, and the remaining groups received a single high-fat, high-fructose diet (HFDF). Three of the HFDF groups received NAM treatment (5, 10, and 15 mM) in drinking water for 16 weeks (5 h/day). While HDL-C and oxidative stress were measured in serum samples, oxidative stress markers, and the gene expression and protein levels of ABCA1 were quantified in liver samples. The HDL-C level altered by the HFDF was improved by treatment with NAM. Furthermore, NAM reduces systemic lipid peroxidation levels and enhances the hepatic antioxidant response affected by the HFDF. In addition, NAM modulates the hepatic ABCA1 gene expression and protein level, altered by the HFDF. Our results suggest that NAM may modify the serum HDL-C level by an improvement of antioxidant response, and a possible modulation of the hepatic ABCA1 gene and protein expression. Further metabolic and molecular studies are needed to support the potential therapeutic role of NAM to prevent or treat lipid alterations promoted by a hypercaloric diet. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver disorders worldwide and can lead to inflammation, fibrosis, and liver cancer. To better understand the impact of an unbalanced hypercaloric diet on liver phenotype in impaired autophagy, the study compared C57BL/6J wild type (WT) and MAPK15-ERK8 knockout (KO) male mice with C57BL/6J background fed for 17 weeks with “Western-type” (WD) or standard diet (SD). Liver features were monitored in vivo by high-frequency ultrasound (HFUS) using a semi-quantitative and parametric assessment of pathological changes in the parenchyma complemented by computer-aided diagnosis (CAD) methods. Liver histology was considered the reference standard. WD induced liver steatosis in both genotypes, although KO mice showed more pronounced dietary effects than WT mice. Overall, HFUS reliably detected steatosis-related parenchymal changes over time in the two mouse genotypes examined, consistent with histology. Furthermore, this study demonstrated the feasibility of extracting quantitative features from conventional B-mode ultrasound images of the liver in murine models at early clinical stages of MASLD using a computationally efficient and vendor-independent CAD method. This approach may contribute to the non-invasive characterization of genetically engineered mouse models of MASLD according to the principles of replacement, reduction, and refinement (3Rs), with interesting translational implications. Full article

Background/Objectives: Alcohol use disorder (AUD) is a major public health issue with rising global occurrence and metabolic consequences. Modeling the addictive behaviors associated with AUD remains inadequate and elusive. Even more so, models that are representative of AUD in concert with excessive caloric intake are limited. Some consequences of chronic alcohol use overlap with the metabolic phenotype of hypercaloric diets. Recently characterized metabolic dysfunction-associated steatotic liver disease with increased alcohol intake (MetALD) helps to differentiate these conditions. This study aims to investigate metabolic phenotypes and gene expression alterations in MetALD mice that are grouped by alcohol preference based on blood phosphatidylethanol levels and alcohol consumption. Methods: Mice were fed high-fat and chow diets, with water and 10% EtOH, for 13 weeks. mRNA sequencing was performed across multiple tissues including brain, liver, skeletal muscle, ileum, and white adipose tissue, and gut microbiome diversity was evaluated via 16S sequencing. Results: Key findings included reduced glucagon in alcohol-preferring mice with no significant differences in dyslipidemia and hepatic steatosis. Additionally, we observed reduced gut microbiome diversity and Wnt signaling with elevated acute-phase response genes in ileum tissue. Reduced Wnt and Hippo signaling in the brain and liver, respectively, was also revealed. Other gene ontologies discovered included increased neural inflammation and adipose mitochondrial translation. Nek3, Ntf3, Cux1, and Irf6 expression changes were shared across at least three tissues and may be potential biomarkers of alcohol addiction. Conclusions: This novel model assists future intervention research in the characterization of MetALD and identifies potential biomarkers of alcohol preference. Full article

Background/Objectives: Obesity is the primary risk factor for the development of chronic degenerative diseases. Multidisciplinary treatments target multiple pathologies associated with obesity. In this study, a potential adjuvant therapy was evaluated by combining extracts from Hibiscus sabdariffa and Zingiber officinale. These extracts were used in both a simple and liposomal suspension, the latter aimed at enhancing the activity of phenolic compounds and determining various metabolic benefits. Methods: In this research, the use of biotechnological approaches for the development of a liposomal suspension formulation with appropriate characteristics of stability, particle size, polydispersity index, concentration, and zeta potential induced an effective reduction in body weight and epididymal fat in a murine obesity model over 8 and 45 days. Results: Treatment with the liposomal suspension reduced variables in the lipid profile, aspartate aminotransferase activity, and energy expenditure, while also promoting an increase in locomotor activity. Conclusions: Therefore, it is suggested that the liposomal suspension represents an alternative for obesity treatment and the reduction of cardiovascular risks. Full article

Background/Objectives: Argania spinosa L. Skeels is a Moroccan endemic plant widely used by the local population as folk medicine. This study aimed to investigate the effects of Argan fruit pulp on lipid metabolism disorders and liver steatosis in hypercaloric diet-fed mice. Methods: Animals were treated with the Argan fruit pulp extract and its fractions for 12 weeks at 100 and 200 mg Kg⁻¹ BW daily. The analysis was conducted on lipid levels in plasma, liver, feces, and bile as well as on glycemia. The liver glutathione, malondialdehyde, and antioxidant enzyme activities were assessed. The hepatic steatosis was evaluated by measuring transaminases and alkaline phosphatase activities and examining histological sections. The polyphenol profiles were determined using HPLC-DAD. Possible underlying mechanisms in the hypolipidemic and hepatoprotective activities were predicted by molecular docking. Results: The crude extract and its aqueous fraction (rich in protocatechuic and gallic acids) significantly restored plasma lipids and glucose levels. Indeed, total cholesterol level (TCHO) was decreased in the liver but increased in bile and feces. The treatment also reduced body weight and liver and adipose tissue mass and prevented liver steatosis. The ethyl acetate fraction exhibited no effect on lipid metabolism but significantly prevented liver oxidative stress. The crude extract and its fractions appear to be nontoxic (LD50 > 5000 mg Kg⁻¹) in mice. The phenolic acids demonstrated strong binding affinity to key targets involved in regulating lipid homeostasis, including ABCA-1, LXR, CYP7A1, HMH-CoA reductase, and PCSK-9. However, the identified flavonoids exhibited high affinities to targets involved in oxidative stress defense (SOD, CAT, and CYP2E1). Conclusions: The Argan fruit pulp, particularly its polyphenols, could be a promising natural approach for preventing cardio-metabolic diseases by improving lipid metabolism and reducing liver oxidative stress. Full article

Introduction: Consuming hypercaloric diets during pregnancy induces metabolic, immune, and maternal intestinal dysbiosis disorders. These conditions are transferred to the offspring through the placenta and breastfeeding, increasing susceptibility to metabolic diseases. We investigated the effect of L. rhamnosus GG supplementation on offspring maternally programmed with a hypercaloric diet. Methods: Our study involved sixteen female Wistar rats aged ten weeks, which were divided into four groups based on their diets: control (Ctrl), cafeteria (CAF), control + probiotic (PRO), and cafeteria + probiotic (CPRO). The control + probiotic and cafeteria + probiotic groups received a daily oral administration of 250 μL of L. rhamnosus GG cell suspension (equivalent to 10⁹ UFC) for nine weeks. The body weight of the animals was recorded weekly, and their food intake was monitored every 24 h. An oral glucose tolerance test was conducted on the offspring at seven weeks of age. At the ninth week of age, animals were euthanized, and blood, tissues, and organs were collected. Results: Maternal supplementation with L. rhamnosus GG decreased food intake and the average birth weight, improved glucose sensitivity, and lowered the levels of LDL, cholesterol, triglycerides, and mesenteric adipose tissue in offspring compared with the control and cafeteria groups. Conclusions: Our findings indicate that supplementing with LGG during maternal programming could protect offspring from metabolic disruptions caused by a hypercaloric maternal diet. Full article

Phytosomes are used as vehicles that carry plant extracts. They exhibit biological activities and possess better bioavailability, bioabsorption, and lower toxicity than drugs. Obesity is an inflammatory state in which oxidative stress is present, which triggers severe effects on the body’s organs. This study aimed to evaluate the impact of the extract and phytosomes of Callistemon citrinus on oxidative stress and inflammation in the liver and heart of Wistar rats fed with a high-fat-fructose diet. Phytosomes containing the extract of leaves of C. citrinus were prepared. The antioxidant, pro-inflammatory enzymes, and biomarkers of oxidative stress were evaluated. Among the groups, only the high-fat-fructose group presented an increase in the COX-2, 5-LOX, and MPO inflammatory enzymes, while the XO enzyme exhibited decreased activity. The groups were fed a hypercaloric diet for 15 weeks while orlistat, C. citrinus extract, and phytosomes were administered at three different concentrations, exhibiting enzyme activities similar to those of the control group. It was also observed that the lowest concentration of phytosomes had a comparable effect to the other concentrations. Callistemon citrinus extract can modulate the activities of enzymes involved in the inflammation process. Furthermore, small doses of phytosomes can serve as anti-inflammatory agents. Full article

Protium heptaphyllum (P. heptaphyllum), popularly known as “almacega” or “white pitch”, is widely used in folk medicine due to its antioxidant, anti-inflammatory and healing properties, attributed to its richness in flavonoids and terpenes. Therefore, this study aimed to evaluate the effects of treatment for 28 days with liposomes containing P. heptaphyllum leaf extract in obese animals. Male Wistar rats, subjected to a hypercaloric diet for 8 weeks to induce obesity (hypercaloric chow and water enriched with 30% sucrose, ad libitum), were treated with the plant formulation (1 mg kg⁻¹day⁻¹, via gavage) for 28 days. The study investigated morphological, metabolic, redox state, immunological and histological parameters in adipose and liver tissue. Rats were divided into four groups: control (C), liposomes with extract (H), obese (O) and obese treated with liposomes containing extract (OH). The results indicated that the obese group (O) presented weight gain, hepatic steatosis and alterations in metabolic and inflammatory parameters. However, treatment with liposomes (OH) reduced glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine and the lipid profile. In adipose tissue, the OH group showed decreased superoxide dismutase (SOD) activity and increased glutathione S-transferase (GST) activity, in contrast to the effects observed in liver GST. In the analysis of thiobarbituric-acid-reactive substances (TBARS), it was possible to observe an increase in all groups in adipose tissue and in group O in liver tissue, in addition to a reduction in TBARS in group OH in the liver, indicating modulation of oxidative stress. The treatment also increased the concentration of IL-10 and IL-17 in the liver and decreased that of IL-6 in adipose tissue. After 28 days of treatment, these results point to the therapeutic potential of treatment with P. heptaphyllum, not necessarily only against obesity, but also an effect per se of the liposomes, possibly due to the high concentration of flavonoids present in the plant extract. Full article

This study investigated the potential of chicken byproduct hydrolysates (CBH) characterized by a mixture of low-molecular-weight peptides (<1.35 kDa) and larger peptides (<17.5 kDa) as a treatment for metabolic syndrome (MS), from a histological and histopathological point of view. This study aimed to evaluate the effects of CBH obtained using plant proteases (BP: B. pinguin, BK: B. karatas, BRO: bromelain) on the histological and histopathological analysis of the liver and kidney in an MS-induced murine model. Methods: Thirty adult male Wistar rats were randomly assigned to six groups (n = 5): (1) standard diet (STD); (2) MS with a hypercaloric diet (MS + HC); (3) CBH-BP (200 mg/kg of body weight); (4) CBH-BK (200 mg/kg of body weight); (5) CBH-BRO (200 mg/kg of body weight); (6) carnosine (CAR) 50 mg/kg of body weight. Liver and kidney samples were processed by conventional hematoxylin and eosin (H&E) histological techniques, Masson’s trichrome stain (MTS), and the periodic acid–Schiff (PAS) histochemical method. A scoring scale was used for the histopathological evaluation with scores ranging from 0 (normal tissue) to 4 (severe damage). Results: CBHs demonstrated a significant therapeutic effect (p < 0.05) on hepatic and renal morphological alterations induced by MS. Hepatic scores for lipid inclusions, vascular congestion, and cellular alteration were all reduced to below two. Similarly, renal scores for tubular degeneration, vascular congestion, and dilation of Bowman’s space were also decreased to less than two. The therapeutic efficacy of CBHs was comparable to that of the positive control, CAR (β-alanyl-L-histidine). Conclusions: CBH-BP, CBH-BK, and CBH-BRO treatments reduced morphological alterations observed in liver and kidney tissues, which is relevant since from a histological and histopathological point of view, it allows us to understand at the cellular and tissue level the effects that these treatments can have on a living organism, indicating a potential to improve organ health in people with MS. Full article

Obesity is a global health problem and is increasing in prevalence in most countries. Although obesity affects all age groups, children are the most vulnerable sector. Functional foods are novel formulated foods containing substances (i.e., nutrients, phytochemicals, probiotics, etc.) that have potential health-enhancing or disease-preventing value. The research objective was to study the possible beneficial effects of providing a functional food made with amaranth flour, chia seed, and curcumin extract on the metabolism and behavior of a rat model of childhood obesity. Male Wistar rat pups from two litters of different sizes, a normal litter (NL) (10 pups) and a small litter (SL) (4 pups), were used. After weaning, the rats were fed a hypercaloric diet (HD) or an HD supplemented with the functional food mixture. Body weight and energy intake were measured for seven weeks, and locomotor activity, learning, and memory tests were also performed. At the end of the experiment, glucose and lipid metabolism parameters were determined. The results showed that in this model of obesity produced by early overfeeding and the consumption of a hypercaloric diet, anxiety-like behaviors and metabolic alterations occurred in the rat offspring; however, the provision of the functional food failed to reduce or prevent these alterations, and an exacerbation was even observed in some metabolic indicators. Interestingly, in the NL rats, the provision of the functional food produced some of the expected improvements in health, such as significant decreases in body weight gain and liver cholesterol and non-significant decreases in adipose tissue and leptin and insulin serum levels. Full article

Increased inflammation is associated with the pathogenesis of heart failure (HF). Increased circulating levels of cytokines have been previously reported and generally associated with worse clinical outcomes. In this context, the modulation of inflammation-related parameters seems to be a reasonable therapeutic option for improving the clinical course of the disease. Based on this, we aimed to compare changes in circulating cytokines when Mediterranean diet alone or in combination with hypercaloric, hyperproteic oral nutritional supplements (ONS), enriched with omega−3 (n−3) polyunsaturated fatty acids were administered to patients with HF. Briefly, patients were randomly assigned to receive Mediterranean Diet (control group) vs. Mediterranean Diet plus ONS (intervention group). We observed increased circulating levels of IL-6, IL-8, MCP-1 and IP-10. MCP-1 and IL-6 were associated with overweight and obesity (p = 0.01–0.01–0.04, respectively); IL-6 and IL-8 were positively correlated with fat mass and CRP serum levels (p = 0.02–0.04, respectively). Circulating levels of IL-8 significantly decreased in all patients treated with the Mediterranean diet, while IL-6 and IP-10 only significantly decreased in patients that received plus ONS. In the univariate analysis, MCP-1 and its combination with IL-6 were associated with increased mortality (p = 0.02), while the multivariate analysis confirmed that MCP-1 was an independent factor for mortality (OR 1.01, 95%ci 1.01–1.02). In conclusion, nutritional support using hypercaloric, hyperproteic, n-3 enriched ONS in combination with Mediterranean Diet was associated with decreased circulating levels of some cytokines and could represent an interesting step for improving heart functionality of patients with HF. Full article

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain–gut–liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain–gut–liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines. Full article

Weight cycling is a major challenge in obesity management. Caloric restriction is known to promote this phenomenon, but the impact of macronutrient changes during dieting remains unclear. This study aimed to determine the role of macronutrient changes in weight maintenance without caloric restriction by alternating between two hypercaloric diets: a high-carbohydrate, high-fat Western diet (WD) and a low-carbohydrate, high-fat diet (LCHDF). Obesity was induced in 8-week-old C57BL/6 male mice by 10 weeks of WD feeding. Then, the mice were subjected to 12 weeks of LCHFD interspersed with WD (I-WD), 3 periods of 2-week LCHFD followed by 2 periods of 3-week WD, or 12 weeks of continuous WD (C-WD). C-WD and I-WD mice were compared to standard diet (SD) mice. In the I-WD group, each LCHFD period decreased weight gain, but mice regained weight after WD resumption. I-WD mice exhibited obesity, dyslipidemia, and glucose intolerance, similarly to the C-WD mice. I-WD mice also developed nonalcoholic steatohepatitis, associated with an increase in type-III collagen gene expression and a decrease in FGF21 protein levels, in comparison with SD. I-WD mice developed weight cycling despite maintaining a high caloric consumption, suggesting that changes in macronutrients during dieting are also a trigger of weight regain. Full article