Metabolic Health Research Articles

The role of brown adipose tissue in metabolic health.

The role of brown adipose tissue in metabolic health.

The gut metabolome in a cohort of pregnant and lactating women from Antioquia-Colombia

Nutrition during the perinatal period is an essential component of health and one that can severely impact the correct development of a human being and its overall condition, in all the subsequent stages of life. The availability of several compounds, mainly macronutrients and micronutrients, plays a key role in the balanced nutrition of both mother and baby and is a process with direct relation to the gut microbiome. Thus, we hereby refer to the set of small molecules derived from gut microbiome metabolism as the gut metabolome. These continuous processes occurring in the gut of a gestating or lactating mother related to microbial communities and nutrients, can be revealed by metabolomics. In this study, we explore for the first time the gut metabolome of pregnant and lactating women, from our region of Antioquia-Colombia, applying untargeted metabolomics by LC-QTOF-MS, and molecular networking. Regarding the gut metabolome composition of the cohort, we found, key metabolites that can be used as biomarkers of microbiome function, overall metabolic health, dietary intake, pharmacology, and lifestyle. In our cohort, pregnant women evidenced a significantly higher abundance of prostaglandins, alkaloids, corticosteroids, organosilicons, and natural toxins, while in lactating women, lipids stand out. Our results suggest that unveiling the metabolic phenotype of the gut microbiome of an individual, by untargeted metabolomics, allows a broad visualization of the chemical space present in this important niche and enables the recognition of influential indicators of the host’s health status and habits, especially of women during this significant perinatal period. This study constitutes the first evidence of the use of untargeted LC-QTOF-MS coupled with molecular networking analysis, of the gut microbiome in a Colombian cohort and establishes a methodology for finding relative abundances of key metabolites, with potential use in nutritional and physiological state assessments, for future personalized health and nutrition practices.

Gender Differences in the Impact of a High-Fat, High-Sugar Diet in Skeletal Muscles of Young Female and Male Mice

In the context of the increasing number of obese individuals, a major problem is represented by obesity and malnutrition in children. This condition is mainly ascribable to unbalanced diets characterized by high intakes of fat and sugar. Childhood obesity and malnutrition are not only associated with concurrent pathologies but potentially compromise adult life. Considering the strict correlation among systemic metabolism, obesity, and skeletal muscle health, we wanted to study the impact of juvenile malnutrition on the adult skeletal muscle. To this aim, 3-week-old C56BL/6 female and male mice were fed for 20 weeks on a high-fat. high-sugar diet, and their muscles were subjected to a histological evaluation. MyHCs expression, glycogen content, intramyocellular lipids, mitochondrial activity, and capillary density were analyzed on serial sections to obtain the metabolic profile. Our observations indicate that a high-fat, high-sugar diet alters the metabolic profile of skeletal muscles in a sex-dependent way and induces the increase in type II fibers, mitochondrial activity, and lipid content in males, while reducing the capillary density in females. These data highlight the sex-dependent response to nutrition, calling for the development of specific strategies and for a systematic inclusion of female subjects in basic and applied research in this field.

Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis

IntroductionThe branched-chain amino acids (BCAAs) are essential to mammalian growth and development but aberrantly elevated in obesity and diabetes. Each BCAA has an independent and specific physio-biochemical effect on the host. However, the exact molecular mechanism of the detrimental effect of valine on metabolic health remains largely unknown.Methods and resultsThis study showed that for lean mice treated with valine, the hepatic lipid metabolism and adipogenesis were enhanced, and the villus height and crypt depth of the ileum were significantly increased. Transcriptome profiling on white and brown adipose tissues revealed that valine disturbed multiple signaling pathways (e.g., inflammation and fatty acid metabolism). Integrative cecal metagenome and metabolome analyses found that abundances of Bacteroidetes decreased, but Proteobacteria and Helicobacter increased, respectively; and 87 differential metabolites were enriched in several molecular pathways (e.g., inflammation and lipid and bile acid metabolism). Furthermore, abundances of two metabolites (stercobilin and 3-IAA), proteins (AMPK/pAMPK and SCD1), and inflammation and adipogenesis-related genes were validated.DiscussionValine treatment affects the intestinal microbiota and metabolite compositions, induces gut inflammation, and aggravates hepatic lipid deposition and adipogenesis. Our findings provide novel insights into and resources for further exploring the molecular mechanism and biological function of valine on lipid metabolism.

Impact of increased protein intake in older adults: a 12-week double-blind randomised controlled trial.

Emerging evidence suggests health-promoting properties of increased protein intake. There is increased interest in plant protein but a dearth of information in relation to its impact on muscle function. The objective of the present work was to examine the impact of intake of different types of proteins on muscle functional parameters including handgrip strength, biomarkers of metabolic health, sleep quality and quality of life in a group of older adults. Healthy men and women aged 50years and older entered a double-blinded, randomised, controlled nutritional intervention study with three parallel arms: high plant protein, high dairy protein and low protein. Participants consumed once daily a ready-to-mix shake (containing 20g of protein in high protein groups) for 12weeks. Changes in handgrip and leg strength, body composition, metabolic health, quality of life and sleep quality were analysed by linear mixed models in an intention-to-treat approach. Eligible participants (n= 171) were randomly assigned to the groups (plant: n= 60, dairy: n= 56, low protein: n= 55) and 141 completed the study. Handgrip strength increased after the intervention (Ptime= 0.038), with no significant difference between the groups. There was no significant difference between groups for any other health outcomes. In a population of older adults, increasing protein intake by 20g daily for 12weeks (whether plant-based or dairy-based) did not result in significant differences in muscle function, body composition, metabolic health, sleep quality or quality of life, compared with the low protein group.

Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

Evaluation of metabolic changes in clinic attendees with therapeutic carbohydrate restriction

Background: Obesity and related metabolic health disorders are major clinical problems that have become increasingly prevalent worldwide.Aim: This before-after study examined the impact of therapeutic carbohydrate restriction (TCR) in managing metabolic health and promoting weight loss in a clinical setting using indirect calorimetry (IC).Setting: Data were collected from medical records obtained from a specialised allied health clinic focusing on metabolic health.Methods: The study analysed retrospective data from 202 overweight or obese participants (77% female, mean age 47.3) who received TCR as part of a behavioural modification programme involving multiple visits where their lifestyle, body composition and respiratory quotient (RQ), a key indicator of fat oxidation were recorded.Results: The study found that TCR improved fat oxidation in 84% of participants at short term visit (around 2 weeks), with an average weight loss of 1.8 kg. At medium term visit (around 12 weeks), 82% of participants maintained an increase in fat oxidation rate, with an average weight loss of 3.9 kg. In addition, among those with recorded body composition and waist circumference, 71% of weight lost was from fat, with an average reduction of 4.9 cm in waist measurements.Conclusion: This real-world study suggests that personalised TCR guided by IC can be an effective strategy for improving metabolic flexibility to help manage excess weight and related co-morbidities in a free-living population. Further research is needed to examine the long-term effects of TCR using this approach.Contribution: The utilisation of IC allows for the examination of individual shifts and improvements in metabolism among patients undergoing TCR.

The impact of time-restricted eating on health-related quality of life: a systematic literature review.

Time-restricted eating (TRE) is a novel dietary intervention shown to facilitate weight loss and improve metabolic health. However, like any dietary intervention, long-term success largely depends on individual adherence, which can be influenced by whether the intervention impacts the individual's health-related quality of life (HR-QoL). Despite the growing body of research investigating TRE as a dietary approach and its potential impact on HR-QoL in adults, to date there has been no systematic review to summarize these findings. To examine the impact of TRE on HR-QoL in adults. All randomized controlled trials, pre-post and pilot/feasibility studies were searched in PubMed, EMBASE via Ovid, CINAHL, Cochrane Library, and PsycINFO via Ovid until March 20, 2023. Two researchers were involved in the screening and paper selection process. A single researcher extracted all relevant data from eligible studies. Overall, 10 studies were eligible for inclusion in this systematic review. Four studies reported improvements in overall HR-QoL scores among participants with type 2 diabetes, middle-aged women with obesity, generally healthy adults, and generally healthy adult employees. Three studies reported significant and nonsignificant improvements in some domains of HR-QoL assessment tools among overweight, sedentary older adults, overweight or obese adults, and 24-hour shift workers. No studies reported that TRE adversely affected HR-QoL. Improvements in HR-QoL appeared to occur primarily at 12 weeks/3 months. There was no clear relationship between HR-QoL scores and TRE protocol, additional study outcomes, participant health status, age, or adherence. Although further research is required to elucidate the impact of TRE on HR-QoL, the findings reveal that no studies show that TRE adversely affects HR-QoL. Open Science Framework (OSF) (The Impact of Time-Restricted Eating on Health-Related Quality of Life: A Systematic Review; https://doi.org/10.17605/OSF.IO/9NK45).

Blood Lipids, Lipoproteins, and Apolipoproteins With Risk of Coronary Heart Disease: A Prospective Study Among Racially Diverse Populations.

Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied. We conducted nested case-control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1-SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1-SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate <0.05), including apolipoprotein B100 to apolipoprotein A1 ratio (OR, 1.57 [95% CI, 1.45-1.7]), low-density lipoprotein-triglycerides (OR, 1.55 [95% CI, 1.43-1.69]), and apolipoprotein B (OR, 1.49 [95% CI, 1.37-1.62]). All these associations were significant and consistent across racial groups and other subgroups defined by age, sex, smoking, obesity, and metabolic health status, including individuals with normal levels of conventionally measured lipids. Our study highlighted several lipoprotein biomarkers, including apolipoprotein B/ apolipoprotein A1 ratio, apolipoprotein B, and low-density lipoprotein-triglycerides, strongly and consistently associated with incident CHD. Our results suggest that comprehensive lipoprotein measures may complement the standard lipid panel to inform CHD risk among diverse populations.

The Potential Role of the Ketogenic Diet in Serious Mental Illness: Current Evidence, Safety, and Practical Advice

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics the physiological state of fasting. The potential therapeutic effects in many chronic conditions have led to the gaining popularity of the KD. The KD has been demonstrated to alleviate inflammation and oxidative stress, modulate the gut microbiota community, and improve metabolic health markers. The modification of these factors has been a potential therapeutic target in serious mental illness (SMI): bipolar disorder, major depressive disorder, and schizophrenia. The number of clinical trials assessing the effect of the KD on SMI is still limited. Preliminary research, predominantly case studies, suggests potential therapeutic effects, including weight gain reduction, improved carbohydrate and lipid metabolism, decrease in disease-related symptoms, increased energy and quality of life, and, in some cases, changes in pharmacotherapy (reduction in number or dosage of medication). However, these findings necessitate further investigation through larger-scale clinical trials. Initiation of the KD should occur in a hospital setting and with strict care of a physician and dietitian due to potential side effects of the diet and the possibility of exacerbating adverse effects of pharmacotherapy. An increasing number of ongoing studies examining the KD’s effect on mental disorders highlights its potential role in the adjunctive treatment of SMI.

Landscape of the gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health

ObjectiveThe remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of...

Effect of a higher protein diet and lifestyle camp intervention on childhood obesity (The COPE study): results from a nonrandomized controlled trail with 52-weeks follow-up

Abstract Purpose In adults, diets rich in protein seem beneficial in relation to satiety, weight loss, and weight management; however, studies investigating dietary protein and weight development in children are scarce and inconsistent. This nonrandomized controlled trial aimed to investigate the effect of a higher protein diet during lifestyle intervention on anthropometry and metabolic biomarkers in children with overweight and obesity. Methods Children (n:208) were recruited from two multicomponent lifestyle camps. One camp was assigned as the intervention group. In the intervention group, carbohydrates-rich foods at breakfast and two in-between-meals were replaced with protein-containing foods to increase the amount of protein from ~ 10–15 energy percent (E%) per day to ~ 25E% per day. Other components were similar between groups. Anthropometry and biochemical measurements were collected at baseline, 10 weeks (after camp) and 52 weeks. Results The intervention group had a non-significant improvement in BMI-SDS (− 0.07 SD (− 0.19; 0.05), p = 0.24) compared to the control group, but in general, there was no effect of a higher protein diet on anthropometry and metabolic biomarkers. Overall, 10 weeks at camp resulted in a more favorable body composition [− 6.50 kg (p &lt; 0.00), − 0.58 BMI-SDS (p &lt; 0.00), and − 5.92% body fat (p &lt; 0.00)], and improved metabolic health, with most changes maintained at 52 weeks. Conclusion A higher protein diet had no significant effect on body composition and metabolic health; however, these lifestyle camps are an efficiatious treatment strategy for childhood obesity. Clinical trial registration: clinicaltrials.gov with ID: NCT04522921. Preregistered August 21st 2020.

Caloric restriction mitigates age-associated senescence characteristics in subcutaneous adipose tissue-derived stem cells.

Adipose tissue regulates metabolic balance, but aging disrupts it, shifting fat from insulin-sensitive subcutaneous to insulin-resistant visceral depots, impacting overall metabolic health. Adipose-derived stem cells (ASCs) are crucial for tissue regeneration, but aging diminishes their stemness and regeneration potential. Our findings reveal that aging is associated with a decrease in subcutaneous adipose tissue mass and an increase in the visceral fat depots mass. Aging is associated with increase in adipose tissue fibrosis but no significant change in adipocyte size was observed with age. Long term caloric restriction failed to prevent fibrotic changes but resulted in significant decrease in adipocytes size. Aged subcutaneous ASCs displayed an increased production of ROS. Using mitochondrial membrane activity as an indicator of stem cell quiescence and senescence, we observed a significant decrease in quiescence ASCs with age exclusively in subcutaneous adipose depot. In addition, aged subcutaneous adipose tissue accumulated more senescent ASCs having defective autophagy activity. However, long-term caloric restriction leads to a reduction in mitochondrial activity in ASCs. Furthermore, caloric restriction prevents the accumulation of senescent cells and helps retain autophagy activity in aging ASCs. These results suggest that caloric restriction and caloric restriction mimetics hold promise as a potential strategy to rejuvenate the stemness of aged ASCs. Further investigations, including in vivo evaluations using controlled interventions in animals and human studies, will be necessary to validate these findings and establish the clinical potential of this well-established approach for enhancing the stemness of aged stem cells.

Interaction of serotonin/GLP-1 circuitry in a dual preclinical model for psychiatric disorders and metabolic dysfunction

Isolation of rodents throughout adolescence is known to induce many behavioral abnormalities which resemble neuropsychiatric disorders. Separately, this paradigm has also been shown to induce long-term metabolic changes consistent with a pre-diabetic state. Here, we investigate changes in central serotonin (5-HT) and glucagon-like peptide 1 (GLP-1) neurobiology that dually accompany behavioral and metabolic outcomes following social isolation stress throughout adolescence. We find that adolescent-isolation mice exhibit elevated blood glucose levels, impaired peripheral insulin signaling, altered pancreatic function, and fattier body composition without changes in bodyweight. These mice further exhibited disruptions in sleep and enhanced nociception. Using bulk and spatial transcriptomic techniques, we observe broad changes in neural 5-HT, GLP-1, and appetitive circuits. We find 5-HT neurons of adolescent-isolation mice to be more excitable, transcribe fewer copies of Glp1r (mRNA; GLP-1 receptor), and demonstrate resistance to the inhibitory effects of the GLP-1R agonist semaglutide on action potential thresholds. Surprisingly, we find that administration of semaglutide, commonly prescribed to treat metabolic syndrome, induced deficits in social interaction in group-housed mice and rescued social deficits in isolated mice. Overall, we find that central 5-HT circuitry may simultaneously influence mental well-being and metabolic health in this model, via interactions with GLP-1 and proopiomelanocortin circuitry.

Short-term high-calorie high-fat feeding induces hyperinsulinemia and blunts skeletal muscle microvascular blood flow in healthy humans.

Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and pre-diabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF prior to impairing insulin-stimulated glucose disposal. It is not known if this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention (+52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 years). Metabolic health and vascular responses to a mixed meal challenge (MMC) were measured at pre- (day 0), mid- (day 4) and post-intervention (day 8). There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and post-intervention. Compared to pre-intervention there was a significant increase in insulin (but not glucose) total area under the curve, in response to the MMC at mid-intervention (p=0.041) and at post-intervention (p=0.028). Unlike at pre- and mid-intervention, at post-intervention muscle MBF decreased at 60 min (p=0.024) and 120 min (p=0.023) following the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 mins (p<0.001) and 120 mins (p<0.001) following the MMC at pre-, mid- and post-intervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses.

Are Young People with Turner Syndrome Who Have Undergone Treatment with Growth and Sex Hormones at Higher Risk of Metabolic Syndrome and Its Complications?

Introduction: Metabolic syndrome (MetS), characterized by visceral obesity, glucose abnormalities, hypertension and dyslipidemia, poses a significant risk of diabetes and cardiovascular disease. Turner syndrome (TS), resulting from X chromosome abnormalities, carries health complications. Despite growing evidence of an increased risk of MetS in women with TS, its prevalence and risk factors remain under investigation. These considerations are further complicated by the varying timing and dosages of treatment with growth hormone and sex hormones. Methods: We conducted a cross-sectional study comparing 44 individuals with TS with 52 age-matched control subjects. Growth hormone treatment in the study group was administered for varying lengths of time, depending on clinical response. We collected anthropometric, metabolic, endocrine and body composition data. Statistical analyses included logistic regression. Results: Baseline characteristics, including age, BMI and height, were comparable between the TS and control groups. Hormonally, individuals with TS showed lower levels of testosterone, DHEA-S, and cortisol, as well as elevated FSH. Lipid profiles indicated an atherogenic profile, and the body composition analysis showed increased visceral adipose tissue in those with TS. Other metabolic abnormalities were common in individuals with TS too, including hypertension and impaired fasting glucose levels. The risk of MetS components was assessed in subgroups according to karyotypes: monosomy 45X0 vs. other mosaic karyotypes. Logistic regression analysis showed a significant association between increased visceral adipose tissue in subjects with TS. Those with metabolic complications tended to have less muscle strength compared to those without these complications in both the study and control groups. Conclusions: This study highlights the unique metabolic and cardiovascular risk profile of individuals with TS, characterized by atherogenic lipids, higher levels of visceral adipose tissue and increased metabolic abnormalities. These findings underscore the importance of monitoring metabolic health in individuals with TS, regardless of age, BMI or karyotype, and suggest the potential benefits of lifestyle modification, building more muscle strength, and weight control strategies. Further research is needed to better understand and address the metabolic challenges faced by women with TS.

Mitochondrial calcium regulation of cardiac metabolism in health and disease.

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the mitochondrial Ca2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca2+ homeostasis is critical: insufficient Ca2+ impairs stress adaptation, while Ca2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca2+ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca2+ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms, but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na+-Ca2+ exchanger and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca2+ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.

Assessment of the content of short-chain fatty acids in ulcerative colitis as an indicator of the patient's metabolic health

Numerous studies show that in the pathogenesis of ulcerative colitis (UC), a significant role is played by a change in the diversity of the intestinal microflora, which is associated with fewer bacteria producing short-chain fatty acids (SCFAs). SCFCS affect the differentiation and activation of cells of the immune system, play a protective role in maintaining the integrity of the epithelial barrier, participate in the regulation of intestinal peristalsis and blood supply to its wall, muscle anabolism, bioavailability of amino acids.The aim of the study. To evaluate the content of SCLC in the feces of UC patients with varying degrees of severity of the current attack, as well as to investigate the relationship between the content of SCLC with dietary characteristics, body mass index (BMI), and dyspenia.Materials and methods. The study involved 80 UC patients, conducted a survey, objective examination, filling out medical history and outpatient records, blood and stool sampling. The content of SCLC was determined in feces. The study of nutritional characteristics in patients with UC was conducted using a standardized questionnaire of the WHO CINDI program. Statistical methods: median (Me), upper and lower quartiles (P25, P75) were calculated; Mann-Whitney criterion; Kolmogorov-Smirnov criterion; nonparametric correlation analysis was performed.Results. The absolute content of SCFCS in the feces of patients with UC is lower than the reference values. The relative content of propionic acid in the subgroup with severe attack was significantly lower than in the remission subgroup, in the subgroup with mild and moderate attack of the disease. In patients with body weight deficiency, the relative content of propionic acid is lower than in UC patients with normal or overweight. A positive relationship was found between the total content of SCFCS in feces and the amount of dietary fiber consumed in the form of fruits and vegetables. In patients with dinapenia, the relative content of butyric acid in feces is significantly lower than in patients without dinapenia.

Biological Rhythms, Chrono-Nutrition, and Gut Microbiota: Epigenomics Insights for Precision Nutrition and Metabolic Health

Biological Rhythms, Chrono-Nutrition, and Gut Microbiota: Epigenomics Insights for Precision Nutrition and Metabolic Health

Crithmum maritimum Extract Restores Lipid Homeostasis and Metabolic Profile of Liver Cancer Cells to a Normal Phenotype.

Hepatocellular carcinoma (HCC) is an alarming epidemiological clinical problem worldwide. Pharmacological approaches currently available do not provide adequate responses due to poor effectiveness, high toxicity, and serious side effects. Our previous studies have shown that the wild edible plant Crithmum maritimum L. inhibits the growth of liver cancer cells and promotes liver cell differentiation by reducing lactic acid fermentation (Warburg effect). Here, we aimed to further characterise the effects of C. maritimum on lipid metabolism and markers of cellular metabolic health, such as AMP-activated protein kinase (AMPK), Sirtuin 1 (SIRT1), and Sirtuin 3 (SIRT3), as well as the insulin signalling pathway. To better mimic the biological spectrum of HCC, we employed four HCC cell lines with different degrees of tumorigenicity and lactic acid fermentation/Warburg phenotype. Lipid accumulation was assessed by Oil Red O (ORO) staining, while gene expression was measured by real-time quantitative PCR (RT-qPCR). The activation of AMPK and insulin signalling pathways was determined by Western blotting. Results indicate that C. maritimum prevents lipid accumulation, downregulates lipid and cholesterol biosynthesis, and modulates markers of metabolic health, such as AMPK, SIRT1 and SIRT3. This modulation is different amongst HCC cell lines, revealing an important functional versatility of C. maritimum. Taken together, our findings corroborate the importance of C. maritimum as a valuable nutraceutical, reinforcing its role for the improvement of metabolic health.