Obesity presents a significant global health challenge, prompting the exploration of diverse treatment options [32]. According to previous studies, palmitoleic acid (PA) exhibits diverse metabolic benefits in 3T3-L1 adipocytes and obese mice, including increased glucose uptake, enhanced lipolysis via PPARα activation, and anti-inflammatory effects. PA supplementation also improves white adipocyte function, boosts fatty acid oxidation, and mitigates hepatic steatosis in obese mice [16, 18,19,20]. Thus, the current study, was aimed to investigate the potential therapeutic effects of 7-MEGA™, a purified form of omega-7 containing over 98.5% purity and more than 500 mg/g of PA [25], on both HFD mice and 3T3-L1 adipocytes. 7-MEGATM comprises various fatty acid esters beyond PA (Supplementary Table 1). Individual effects of these esters on obesity have been elucidated in previous studies. For instance, oleic acid has been shown to ameliorate heart conditions by reducing cholesterol levels and inflammation [33]. Additionally, Myristoleic acid has been found to mitigate obesity by activating brown adipose tissue [34]. However, it is important to note that both palmitic acid and myristic acid, as individuals, exhibit adverse metabolic effects that contribute to the development and progression of obesity. These effects can vary depending on factors such as overall dietary composition, metabolic health, and genetic predisposition [35, 36].

Thus, the main objective of this study was to evaluate how 7-MEGA™, as a compound, affects the biology of adipocytes and whether it can help to mitigate the pathophysiology associated with obesity, to evaluate its potential as a functional food, offering health benefits beyond basic nutrition. According to the results from WST-1 assay, 7-MEGA™ demonstrates no significant detrimental impact on adipocyte viability, implying a favorable safety profile in this cellular context. Furthermore, the results of present study showed that 7-MEGA™ treatment inhibits pre-adipocyte differentiation into mature adipocytes in a concentration-dependent manner, suggesting that it may be used as an adipogenesis modulator. This attenuation of adipocyte differentiation was accompanied by a notable reduction in lipid accumulation within the cells, indicative of the efficacy of 7-MEGA™ in mitigating adipocyte hypertrophy and lipid deposition. These findings highlight the intriguing role of 7-MEGA™ in regulating the biology of adipocytes and suggest its potential use as a therapy to treat metabolic dysregulation linked to obesity.

Findings of this study provide more insight into the molecular mechanisms behind the impacts of 7-MEGA™ on the biology of adipocytes and the regulation of lipid metabolism of HFD mice. In particular, the results indicated that higher levels of expression of several key lipogenic and adipogenic markers, such as C/EBPα, PPARγ, SREBP-1, FAS, SCD-1 and ACC in HFD mice and in untreated adipocytes. Since PPARγ is crucial for both lipid metabolism [37] and adipocyte differentiation [38], C/EBPα regulates adipocyte differentiation [39], SREBP-1 is thought to be a transcription factor involved in lipid synthesis [40], FAS contributes to de novo lipogenesis [41], ACC is an essential enzyme in fatty acid synthesis [42], and SCD-1, an enzyme which transforms saturated fatty acids into monounsaturated fatty acids, affecting lipid composition, all of these markers are important for regulating adipogenesis [43]. Following treatment or oral administration of 7-MEGA™, the expression levels of these markers were dramatically lowered, indicating that the supplement may have the ability to inhibit adipogenesis. Furthermore, the expression levels of FABP4, which is primarily expressed in adipocytes, increased in adipocytes and decreased upon 7-MEGA™ treatment implying the potential of 7-MEGA™ to inhibit adipogenesis.

Moreover, PPARα and UCP-1 expressions were at lower levels in obese mice in this investigation. However, the administration of 7-MEGA™ increased their expression. PPARα promotes lipid metabolism and helps to avoid adipogenesis by controlling gene expressions involved in fatty acid oxidation [44]. UCP-1 serves a critical function in thermogenesis, promoting energy expenditure and preventing obesity [45]. The administration of 7-MEGA™ restored their expression indicating that 7-MEGA™ promote energy expenditure and lipid oxidation. These findings imply that 7-mega may improve fatty acid oxidation and thermogenesis to prevent obesity-induced metabolic dysregulation, helping to treat obesity and its related metabolic problems.

Furthermore, according to the results, in HFD mice, 7-MEGA™ treatment led to a concentration-dependent decrease in body weight and food consumption. The observed reduction in food intake among obese mice may be attributed to its potential anti-obesity effects, potentially mediated through mechanisms such as appetite suppression, alteration of metabolic pathways, or modulation of hormonal signalling related to hunger and satiety. All of these results suggest the possibility that 7-MEGA™ might successfully prevent obesity-related weight gain and adiposity by reducing fat formation, decreasing appetite, and possibly preventing the differentiation of adipocytes.

Findings further demonstrated that the HFD group had larger adipocytes, and size was normalized by the administration of 7-MEGA™. The primary cause of this increase in adipocyte size is a condition known as adipocyte hypertrophy, which is resulting from an overabundance of accumulation of triglycerides and other lipids within the adipocytes [30]. Additionally, it was noted that the treatment of 7-MEGA™ caused the steatosis in the liver tissues caused by the accumulation of fat in the livers of obese mice disappeared. Obesity and steatosis are frequently linked [46, 47]. The findings further demonstrated that 7-MEGA™ can lessen the accumulation of fat mass in the adipose tissues of PWAT and SWAT. All of these concentration-dependent effects reflect the possible dose-dependent effectiveness of 7-MEGA™ in the treatment of metabolic disorders associated with fat accumulation and obesity.

In the HFD group, lower levels of adiponectin and higher levels of insulin, leptin, IFN‑γ, TNF‑α, IL‑6 and IL‑1β were observed. On the other hand, the administration of 7-MEGA™ caused these biomarkers to shift, leading to a rise in adiponectin levels and a drop-in insulin, leptin, IFN‑γ, TNF‑α, IL‑6 and IL‑1β. These changes indicate a beneficial shift in the metabolic environment, marked by an increase in anti-inflammatory adiponectin and a decrease in pro-inflammatory cytokines and insulin resistance indicators. More specifically, increased adiponectin indicates greater insulin sensitivity and maybe improved metabolic health, while decreased insulin, leptin, IFN‑γ, TNF‑α, IL‑6 and IL‑1β levels suggest attenuation of inflammation and improved insulin sensitivity [48, 49]. All of these modifications suggest that 7-MEGA™ may be able to reduce metabolic dysregulation linked to obesity by influencing inflammatory pathways and adipokine levels.

As a summary, the aim of this study was to investigate the therapeutic potential of 7-MEGA™ in the management of obesity and related metabolic disorders. The results showed that in HFD mice, 7-MEGA™ administration reduced body weight and food intake along with decreasing the number of primary adipocytes and fat mass accumulation. Additionally, 7-MEGA™ administration resulted in the modulation of key adipogenic and lipogenic markers, including reduced expression levels of PPARγ, FAS, ACC, C/EBPα, SREBP1, and SCD-1, exploring its capacity to mitigate adipocyte differentiation and lipogenesis. Furthermore, 7-MEGA™ treatment reversed the downregulation of thermogenic and fatty acid oxidation indicators, such as UCP-1 and PPARα, and mitigated the dysregulation of adipocyte-specific markers, such as FABP4. This suggests that 7-MEGA™ has a role in increasing energy expenditure and lipid oxidation. In addition, the 7-MEGA™ treatment caused alterations in circulating biomarkers, which showed an elevation in adiponectin levels and a decrease in insulin, leptin, IFN‑γ, TNF‑α, IL‑6 and IL‑1β. These changes suggested an overall improvement in metabolic health and decrease in inflammation. All things considered, this research emphasises the complex ways that 7-MEGA™ affects the biology of adipocytes and the control of metabolism. To completely clarify the therapeutic efficacy of 7-MEGA™ in clinical settings, more research into the molecular processes underlying these reported results is necessary.

Furthermore, the understanding the impact of 7-MEGA™ on adipogenesis in animals on high-fat diets involves considering its potential benefits and risks within the complex framework of metabolic regulation. While the ability of 7-MEGA™ to inhibit adipogenesis offers promise in reducing fat accumulation, especially pertinent in addressing obesity, it is essential to acknowledge the intricate role of adipose tissue in metabolic homeostasis. Adipogenesis is critical for energy balance, lipid metabolism, and hormonal regulation [50]. Disrupting this process entirely could lead to metabolic dysregulation and associated health risks, particularly in individuals already susceptible to metabolic disturbances [51, 52]. Therefore, the use of 7-MEGA™ or similar compounds in animals on high-fat diets demands careful evaluation of both its potential advantages and the broader implications for metabolic health. Further research is necessary to comprehensively understand the effects of inhibiting adipogenesis in these contexts, guiding more informed therapeutic strategies to improve metabolic health in affected populations.

This study benefits from its comprehensive approach to investigating the therapeutic potential of 7-MEGA™ in managing obesity and related metabolic disorders. The research employs a combination of in vivo and in vitro experiments, providing a multifaceted understanding of how 7-MEGA™ influences adipocyte biology and metabolic processes. Additionally, the study utilizes a purified form of omega-7 with high purity, enhancing the reliability and consistency of the results. Moreover, the investigation explores various molecular markers and circulating biomarkers, offering insights into the mechanisms underlying the observed effects of 7-MEGA™. Despite its strengths, this study has several limitations that should be considered. Firstly, the research primarily focuses on animal models and adipocyte cultures, limiting the direct applicability of the findings to human populations. Furthermore, the study lacks long-term follow-up data, making it challenging to assess the sustained efficacy and safety of 7-MEGA™ over extended periods.