Search Results (142)

The global prevalence of obesity and type 2 diabetes mellitus (T2D) has risen in parallel over recent decades. Most individuals diagnosed with T2D exhibit adiposopathy-related diabetes (ARD), a condition characterized by hyperglycemia accompanied by three core features: increased ectopic and visceral fat deposition, dysregulated adipokine secretion favoring a pro-inflammatory state, and insulin resistance. Despite advancements in precision medicine, international guidelines for T2D continue to prioritize individualized therapeutic approaches focused on glycemic control and complications, and many healthcare providers predominantly maintain a glucocentric strategy. This review advocates for an adipocentric treatment paradigm for most individuals with T2D, emphasizing the importance of prioritizing weight loss and visceral fat reduction as key drivers of therapeutic intensification. By combining lifestyle modifications with pharmacological agents that promote weight loss—including SGLT-2 inhibitors, GLP-1 receptor agonists, or dual GLP-1/GIP receptor agonists—and, when appropriate, metabolic surgery, this approach offers the potential for disease remission in patients with shorter disease duration. For others, it enables superior metabolic control compared to traditional glucose-centered strategies while simultaneously delivering cardiovascular and renal benefits. In conclusion, an adipocentric treatment framework for ARD, which represents the majority of T2D cases, effectively integrates glucocentric and cardio-nephrocentric goals. This approach constitutes the optimal strategy for ARD due to its efficacy in achieving disease remission, improving metabolic control, addressing obesity-related comorbidities, and reducing cardiovascular and renal morbidity and mortality. Full article

Hypertension is one of the most common comorbidities in cardiometabolic diseases, affecting nearly one third of adults. As a result, its pathophysiological mechanisms have been studied extensively and are focused around pressure natriuresis, the renin–angiotensin system (RAS), the sympathetic nervous system, oxidative stress, and endothelial dysfunction. Additionally, hypertension secondary to other underlying etiologies also exists. While clinical evidence has clearly shown differences in hypertension development in males and females, relatively little is known about the pathophysiological mechanisms behind these differences. Sex hormones likely play a key role, as they modulate many factors related to hypertension development. In this review, we postulate the potential role for sexually dimorphic fat metabolism in the physiology of hypertension. In brief, estrogen promotes subcutaneous fat deposition over visceral fat and increases in mass via adaptive hyperplasia rather than pathogenic hypertrophy. This adipose tissue subsequently produces anti-inflammatory effects and inhibits metabolic dysfunction-associated fatty liver disease (MAFLD) and RAS activation, ultimately leading to decreased levels of hypertension in pre-menopausal females. On the other hand, androgens and the lack of estrogens promote visceral and ectopic fat deposition, including in the liver, and lead to increased circulating pro-inflammatory cytokines and potentially subsequent RAS activation and hypertension development in males and post-menopausal females. Understanding the sex-specific differences in fat metabolism may provide deeper insights into the patho-mechanisms associated with hypertension and lead to more comprehensive sex-specific care. Full article

Background/Objectives: Obesity is a key factor in metabolic syndrome (MetS) development. Consumption of a high-fat diet (HFD) accelerates the onset of obesity and associated metabolic complications. Protaetia brevitarsis (PB) has been traditionally utilized in Korean medicine for its antioxidant, anti-diabetic, anticancer, and hepatoprotective effects. However, specific effects of PB hydrolysate on skeletal muscles have not been fully elucidated. Therefore, this study sought to assess the influence of PB on HFD-induced MetS, focusing on the lipid metabolism and inflammatory responses mediated by AMP-activated protein kinase activation. Methods: To induce obesity, 6-week-old C57BL/6J mice were maintained on an HFD for 8 weeks, after which PB hydrolysate was orally administered for 16 weeks while the HFD regimen was sustained. A glucose tolerance test was conducted orally to evaluate glucose regulation, and forelimb grip strength was assessed upon completion of the experimental period. Histological assessments, serum biochemical analysis, lipid extraction, Western blot analysis, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were performed following euthanasia. Results: PB significantly reduced ectopic lipid deposition in skeletal muscles, enhanced muscle strength, and improved insulin sensitivity by increasing fatty acid oxidation via AMP-activated protein kinase/carnitine palmitoyltransferase 1 activation and inhibiting lipogenesis via stearoyl-CoA desaturase 1 gene downregulation. Furthermore, PB alleviated HFD-induced low-grade chronic inflammation by decreasing systemic monocyte chemoattractant protein 1 levels, thereby reducing ectopic fat deposition. Conclusions: This study highlights the potential of PB as a nutraceutical to mitigate MetS in HFD-fed mice. Full article

Background/Objectives: Functional probiotics, particularly Lactobacillus delbrueckii subsp. lactis CKDB001, have shown potential as a therapeutic option for metabolic dysfunction-associated steatotic liver disease (MASLD). However, their effects have not been confirmed in in vivo systems. Here, we investigated the effects of L. delbrueckii subsp. lactis CKDB001 on insulin resistance, dyslipidemia, MASLD, and lipid metabolism in a murine model of high-fat diet (HFD)-induced obesity. Methods: The mice were divided into four groups (n = 12 per group)—normal chow diet (NCD), high fat diet (HFD), HFD with L. delbrueckii subsp. lactis CKDB001 (LL), and HFD with resmetirom (positive control (PC), a thyroid receptor β agonist). The experimental animals were fed NCD or HFD for 12 weeks, followed by an additional 12-week oral treatment with LL or resmetirom. Results: LL supplementation reduced body weight, insulin levels, and HOMA-IR compared with those in the HFD group, indicating improved insulin sensitivity. Additionally, LL reduced serum triglyceride (TG) levels without affecting total cholesterol (TC) levels. HFD consumption increased liver weight and hepatic TG and TC levels, indicating ectopic fat accumulation; however, LL supplementation reversed these changes, indicating a liver-specific effect on cholesterol metabolism. Furthermore, LL administration attenuated NAFLD activity scores, reduced hepatic fibrosis, improved liver function markers (aspartate aminotransferase), and enhanced Adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. However, LL did not considerably affect the expression of genes related to lipid metabolism. In epididymal adipose tissue, LL treatment reduced leptin levels but had no effect on adiponectin; additionally, histological analysis showed an increase in adipocyte size, potentially linked to enhanced energy metabolism. Conclusions: Collectively, these findings suggest that LL could be a promising therapeutic candidate for improving insulin sensitivity, reducing hepatic lipid accumulation, and mitigating MASLD. Full article

Consuming a “modern” Western diet and overnutrition may increase insulin secretion. Additionally, nutrition-mediated hyperinsulinemia is a major driver of ectopic fat deposition. The global prevalence of metabolic syndrome is high and growing. Within this context, people with congenital lipodystrophy often experience a severe form of metabolic syndrome. Evidence is increasingly supporting that subtle partial lipodystrophy plays an important role in the development of metabolic syndrome in the general population. In individuals in the general population with subtle partial lipodystrophy, as well as in those with congenital lipodystrophy, the subcutaneous adipose tissues are unable to accommodate surplus energy intake. In both conditions, (excess) fat is directed toward the liver, pancreas, and muscles, where it is deposited as ectopic fat, as this fat can no longer be stored in the “safe” subcutaneous fat depots. Ectopic fat depositions cause insulin resistance in the liver and muscles, as well as β-cell dysfunction in the pancreas. Support of a direct pathological role of ectopic fat deposition in this condition is further provided by the rapid normalization of hepatic insulin sensitivity and improvement in pancreatic β-cell function after marked reductions in ectopic fat depositions. Thus, ectopic fat deposition in the liver, pancreas, and muscles may play a causal role in the pathogenesis of metabolic syndrome even in the general population. As such, the prevention of ectopic fat deposition may reduce the risk of metabolic syndrome and mitigate its effects. Full article

Abstract: Turandot (Tot) family proteins, which are induced via the JAK/STAT pathway after infection, also suppress lymph gland tumors in Drosophila mxc^mbn1 mutant larvae. We investigated the potential role of hemocytes in Tot induction in tumor-bearing mutants via immunostaining and RNAi experiments. Normal hemocytes transplanted into mutant larvae were recruited to the tumor and fat body (FB), suggesting that these cells transmit tumor-related information. The transplanted hemocytes ectopically expressed Unpaired3 (Upd3), which is necessary for the activation of JAK/STAT. Eiger, a Drosophila tumor necrosis factor (TNF) ortholog, was highly expressed in tumors. Depletion of the Eiger receptor in hemocytes reduced Tot levels and eventually enhanced tumor growth. The c-Jun N-terminal kinase (JNK) pathway, acting downstream of the receptor, was also activated in the hemocytes of mutants. Downregulation of the JNK pathway in hemocytes inhibited Tot induction, leading to enhanced tumor growth. These results suggest that upd3 expression in hemocytes depends on the Eiger–JNK pathway. We propose that after Eiger activates the JNK pathway in hemocytes present on the tumor, cells expressing Upd3 are recruited to the FB. Upd3 then activates JAK/STAT to induce the expression of antitumor proteins. This study highlights the intricate communication between tissues via blood cells during tumor suppression. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model. Dasatinib and quercetin were administered to a medaka MASLD model, which was fed a high-fat diet by dissolving them in aquarium water. The results revealed that senescent cells in the liver were increased in the HFD group but improved in the treatment group. Hematoxylin and eosin staining also showed that treatment improved fat deposition in hepatocytes. In addition, TGFβ1, a driver factor of fibrosis, was reduced in the treatment group. Dasatinib and quercetin eliminated senescent cells in MASLD, attenuated fat deposition, and suppressed fibrosis gene expression. The results indicate that dasatinib and quercetin as senolytic drugs are novel therapeutic agents that reduce MASLD. Full article

Background: Obesity, a global disease, can lead to different chronic diseases and a series of social health problems. Lifestyle changes, especially dietary changes, are the most effective way to treat obesity. Euglena, a novel food, has attracted much attention. Previous studies have shown that Euglena is an important modulator of the host immune response. In this study, the effects of Euglena as a nutritional intervention in high-fat-diet-induced obese C57BL/6J mice were investigated regarding adipose tissue accumulation and lipid and glucose metabolism by gavage at the dose of 100 mg/kg bodyweight for 9 weeks. This study is one of the few to investigate, in detail, the preventive effects of dietary Euglena on obesity. Methods: Five-week-old male C57BL/6J mice were fed with a high-fat diet (HFD) to induce obesity. An obesity model was created by feeding the high-fat diet for a period of 10 weeks. Obese mice were randomized into 2 groups with the same mean body weight, and no significant differences were observed between the groups: (1) the mice in the HEG group were maintained on a high-fat diet and daily gavaged with Euglena (100 mg/kg body weight) dissolved in saline (n = 7); and (2) the mice in the HFD group were maintained on a high-fat diet and daily gavaged with saline with the same volume (n = 7). The experiment finished after a nine-week period. Results: The results showed that Euglena could reduce the accumulation of white body fat, including subcutaneous fat and visceral fat, and mainly targeted subcutaneous fat. Euglena also reduced adipocyte particle size expansion, promoted lipolysis in adipose (adipose triglyceride lipase and hormone-sensitive triglyceride lipase) and liver tissue (reduced non-esterified fatty acid content), and improved obesity-induced ectopic fat deposition and glucose tolerance. Conclusions: Our findings suggest that Euglena, as a nutritional intervention in HFDs, efficiently reduces body weight and white adipose tissue deposition. The mechanism of Euglena is mainly though enhancing lipolysis. It is worth noting that Euglena β-glucan recovers the hyperglycemia and accumulation of ectopic fat within the liver induced by HFD. Our study is one of the few studies to report in detail the preventive effects of dietary Euglena on obesity in vivo. This study revealed that Euglena also has an important ameliorative effect on obesity and metabolic disorders, which laid a theoretical foundation for its future application in functional foods. Full article

Body composition analysis focuses on measuring skeletal muscle mass and total body fat. The loss of muscle function and mass is related to clinical conditions such as frailty, increased risk of falls, and prolonged hospitalizations. Despite the relevance of the definition of sarcopenic obesity, there is still a gap in the monitoring of patients who have the combination of sarcopenia and myosteatosis, regardless of the presence of obesity. Therefore, we propose a new nomenclature, steatosarcopenia, a condition characterized by the loss of mass or skeletal muscle strength and performance associated with the excessive deposition of ectopic reserve fat in muscle tissue, in the same individual, not necessarily related to excess fat total body mass. A greater understanding of this condition may assist in developing strategies for preventing and treating metabolic diseases. Full article

Obesity and type 2 diabetes mellitus are global public health issues. Although males show higher obesity and insulin resistance prevalence, current treatments often neglect sex-specific differences. White adipose tissue (WAT) is crucial in preventing lipotoxicity and inflammation and has become a key therapeutic target. Rosiglitazone (RSG), a potent PPARγ agonist, promotes healthy WAT growth and mitochondrial function through MitoNEET modulation. Recent RSG-based strategies specifically target white adipocytes, avoiding side effects. Our aim was to investigate whether sex-specific differences in the insulin-sensitizing effects of RSG exist on WAT during obesity and inflammation. We used Wistar rats of both sexes fed a high-fat diet (HFD, 22.5% fat content) for 16 weeks. Two weeks before sacrifice, a group of HFD-fed rats received RSG treatment (4 mg/kg of body weight per day) within the diet. HFD male rats showed greater insulin resistance, inflammation, mitochondrial dysfunction, and dyslipidemia than females. RSG had more pronounced effects in males, significantly improving insulin sensitivity, fat storage, mitochondrial function, and lipid handling in WAT while reducing ectopic fat deposition and enhancing adiponectin signaling in the liver. Our study suggests a significant sexual dimorphism in the anti-diabetic effects of RSG on WAT, correlating with the severity of metabolic dysfunction. Full article

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [¹⁸F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted. Full article

Background/Objectives: The aim of the present study was to determine the effects of exercise training on ectopic and subcutaneous fat in patients with type 2 diabetes mellitus (T2DM). Methods: Web of Science, PubMed, and Scopus were searched for original articles published through November 2023 that included exercise versus control interventions on body mass (BM), liver fat percentage, visceral fat area (VFA), subcutaneous fat area (SFA), and intramuscular fat volume or mass (IMF) in patients with T2DM. Weighted mean differences (WMDs) for liver fat and BM, standardized mean differences (SMDs) for VFA, SFA, and IMF, and 95% confidence intervals (95% CIs) were determined using random-effects models. Results: Thirty-six studies comprising 2110 patients with T2DM were included in the present meta-analysis. Exercise training effectively reduced BM [WMD = −2.502 kg, p = 0.001], liver fat% [WMD = −1.559%, p = 0.030], VFA [SMD = −0.510, p = 0.001], and SFA [SMD = −0.413, p = 0.001] in comparison to the control. The IMF [SMD = 0.222, p = 0.118] remained unchanged compared to the controls. Subgroup analyses showed that the type of exercise, duration, and body mass index (BMI) of participants were sources of heterogeneity. Conclusions: The current meta-analysis provides strong evidence that exercise training, particularly aerobic and combined (aerobic and resistance) exercise programs, is effective for reducing BM, VFA, and SFA in patients with T2DM. However, aerobic exercise was more effective for reducing liver fat than combined exercise. The beneficial effects of exercise on VFA and SFA reduction, but not liver fat, are associated with weight loss. These findings highlight the importance of including consistent exercise as a key management component for T2DM and associated ectopic fat deposition, with potential long-term benefits for metabolic health. Full article

Nut-based products are a good source of high-quality plant protein in addition to mono- and polyunsaturated fatty acids, and may aid low-glycaemic dietary strategies important for the prevention of type 2 diabetes (T2D). In particular, they may be advantageous in populations susceptible to dysglycaemia, such as Asian Chinese. The present study aimed to compare effects of a higher-protein nut bar (HP-NB, also higher in total fibre and unsaturated fats, comprising mixed almonds and peanuts) vs. an isoenergetic higher-carbohydrate cereal bar (HC-CB) within the diet of 101 Chinese adults with overweight and normo- or hyperglycaemia. Ectopic pancreas and liver fat were characterised using magnetic resonance imaging and spectroscopy (MRI/S) as a secondary outcome. Participants were randomized to receive HP-NB or HC-CB daily as a 1 MJ light meal or snack replacement, in addition to healthy eating advice. Anthropometry and clinical indicators of T2D risk were assessed fasted and during an oral glucose tolerance test (OGTT), pre- and post-intervention. No significant difference was observed between diet groups for body weight, body mass index, waist or hip circumference, blood pressure, glucoregulatory markers, lipid profile or inflammatory markers over 12 weeks (all, p > 0.05). No difference was observed between glycaemic subgroups or those with normal versus high ectopic organ fat. Although HP-NB can attenuate postprandial glycaemia following a meal, no effects were observed for either fasting or glucose-mediated outcomes following longer-term inclusion in the habitual diet of Chinese adults with overweight, including at-risk subgroups. Full article

The worldwide incidence of prediabetes/type 2 has continued to rise the last 40 years. In the same period, the mean daily energy intake has increased, and the quality of food has significantly changed. The chronic exposure of pancreatic β-cells to calorie excess (excessive energy intake) and food additives may increase pancreatic insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing chronic hyperinsulinemia and peripheral insulin resistance. Chronic calorie excess and hyperinsulinemia may promote lipogenesis, inhibit lipolysis and increase lipid storage in adipocytes. In addition, calorie excess and hyperinsulinemia can induce insulin resistance and contribute to progressive and excessive ectopic fat accumulation in the liver and pancreas by the conversion of excess calories into fat. The personal fat threshold hypothesis proposes that in susceptible individuals, excessive ectopic fat accumulation may eventually lead to hepatic insulin receptor resistance, the loss of pancreatic insulin secretion, hyperglycemia and the development of frank type 2 diabetes. Thus, type 2 diabetes seems (partly) to be caused by hyperinsulinemia-induced excess ectopic fat accumulation in the liver and pancreas. Increasing evidence further shows that interventions (hypocaloric diet and/or bariatric surgery), which remove ectopic fat in the liver and pancreas by introducing a negative energy balance, can normalize insulin secretion and glucose tolerance and induce the sustained biochemical remission of type 2 diabetes. This pathophysiological insight may have major implications and may cause a paradigm shift in the management of type 2 diabetes: avoiding/reducing ectopic fat accumulation in the liver and pancreas may both be essential to prevent and cure type 2 diabetes. Full article

Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle changes, including a balanced diet and physical exercise, are necessary to prevent these undesirable changes. Strength training (ST) has been widely used because of the muscle and metabolic benefits it provides. Our study aims to evaluate the effects of ST on hepatic steatosis and insulin resistance in ovariectomized mice fed a high-fat diet (HFD) divided into four groups as follows: simulated sedentary surgery (SHAM-SED), trained simulated surgery (SHAM-EXE), sedentary ovariectomy (OVX-SED), and trained ovariectomy (OVX-EXE). They were fed an HFD for 9 weeks. ST was performed thrice a week. ST efficiently reduced body weight and fat percentage and increased lean mass in OVX mice. Furthermore, ST reduced the accumulation of ectopic hepatic lipids, increased AMPK phosphorylation, and inhibited the de novo lipogenesis pathway. OVX-EXE mice also showed a better glycemic profile, associated with greater insulin sensitivity identified by the euglycemic–hyperinsulinemic clamp, and reduced markers of hepatic oxidative stress compared with sedentary animals. Our data support the idea that ST can be indicated as a non-pharmacological treatment approach to mitigate metabolic changes resulting from menopause. Full article