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Search Results (383)

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Keywords = adipocyte size

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26 pages, 1451 KB  
Systematic Review
Adipocyte Size, Overweight, and Insulin Resistance in Type 2 Diabetes Mellitus and the Impact of Weight Loss: A Systematic Review
by Kuat P. Oshakbayev, Altay N. Nabiyev, Aigul K. Durmanova, Gani M. Kuttymuratov, Timur S. Suleimenov, Nurzhan A. Bikhanov, Alisher S. Idrissov, Guldana Zh. Bazheneyeva, Kenzhekyz Manekenova, Ainur R. Akilzhanova and Bibazhar A. Dukenbayeva
Nutrients 2026, 18(9), 1382; https://doi.org/10.3390/nu18091382 - 28 Apr 2026
Viewed by 1055
Abstract
Background: The impact of overweight and adipocyte size on the development of type 2 diabetes mellitus (T2DM) remains unclear. Aim: We studied (1) the relationship between the state of adipocytes and/or overweight/obesity, the development of T2DM and its clinical and laboratory features; and [...] Read more.
Background: The impact of overweight and adipocyte size on the development of type 2 diabetes mellitus (T2DM) remains unclear. Aim: We studied (1) the relationship between the state of adipocytes and/or overweight/obesity, the development of T2DM and its clinical and laboratory features; and (2) weight loss effect on glycemic level, endogenous hyperinsulinism (HI), insulin resistance (IR), and T2DM. Methods: We designed a systematic review by searching Web of Science, EBSCO, Scopus/ Science-Direct, Google Scholar, PubMed, Cochrane, and Wolter Kluwer for articles published in 26 years (2000–2026). The study was based on a systematic review of 3853 articles published worldwide. Results: In total, 142 full-text articles were assessed for eligibility. As overweight increases, the size of adipose tissue, adipocytes, and cell radius increase. The increase in cell size overloads intracellular transport and internal organs. The development of IR is a conformational change in cellular receptors caused by an excessive increase in cell size. The increase in cell size with overweight gradually leads to hyperglycemia and HI with the development of IR and T2DM. Any targeted intentional weight loss in patients with T2DM improves metabolic and cardiovascular health, reduces blood pressure and blood sugar, and decreases HI, IR, and T2DM. Conclusions: IR is a protective response of cells that prevents oversaturation and overflow. Overweight is an independent risk factor for the development of HI, IR, and T2DM. Targeted weight loss leads to the cure of HI, IR and T2DM. Full article
(This article belongs to the Section Nutrition and Diabetes)
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9 pages, 2384 KB  
Case Report
Large Oral Lipomas: Uncommon Neoplasms in Two Case Reports
by Juraj Brozović, Bruno Vidaković, Barbara Mikulić and Matej Tomas
Dent. J. 2026, 14(4), 244; https://doi.org/10.3390/dj14040244 - 20 Apr 2026
Viewed by 535
Abstract
Background: Oral lipomas are uncommon benign tumors composed of mature adipocytes, accounting for roughly 1% of benign intraoral lesions. Common predilection sites are buccal mucosa, lips, and tongue, presenting as slow-growing, nodular masses, often with a yellow hue. As the size of [...] Read more.
Background: Oral lipomas are uncommon benign tumors composed of mature adipocytes, accounting for roughly 1% of benign intraoral lesions. Common predilection sites are buccal mucosa, lips, and tongue, presenting as slow-growing, nodular masses, often with a yellow hue. As the size of most lesions does not exceed 10 mm, particularly larger lipomas may be misdiagnosed. We present two cases of large oral lipomas. Case reports: Case 1: A 58-year-old male with a painless, sessile nodular mass of approximately 2.5 cm in the left cheek, increasing in size and causing discomfort during mastication. After excision, histopathology revealed mature adipocytes with delicate fibrous septa. Case 2: A 47-year-old female with a tender yellow growth of approximately 2 cm in her lower lip, increasing in size and causing aesthetic problems with functional discomfort. After sharp dissection, the specimen presented acanthotic and parakeratotic epithelium with adipocytic tumorous tissue, permeated by collagenous cords. Conclusions: Oral lipomas are uncommon, mostly asymptomatic benign lesions. Mostly found in the buccal mucosa and lower lip, they can mimic more common growths. When located superficially, a conservative surgical excision leads to resolution with rare recurrences. Histopathological inspection is necessary to confirm the benign nature of the lesion. Full article
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17 pages, 1927 KB  
Article
Direct Measurement of Adipose Thermogenesis by Isothermal Microcalorimetry
by Pauke C. Schots, Devesh Kesharwani, Chad C. Doucette and Aaron C. Brown
Cells 2026, 15(7), 579; https://doi.org/10.3390/cells15070579 - 25 Mar 2026
Viewed by 785
Abstract
Direct measurement of thermogenic heat production remains a major challenge in adipose biology. Isothermal microcalorimetry offers a label-free approach to quantify metabolic heat output, yet key parameters governing its application to adipose tissue remain poorly defined. Here, we systematically evaluate the use of [...] Read more.
Direct measurement of thermogenic heat production remains a major challenge in adipose biology. Isothermal microcalorimetry offers a label-free approach to quantify metabolic heat output, yet key parameters governing its application to adipose tissue remain poorly defined. Here, we systematically evaluate the use of the CalScreener isothermal microcalorimetry platform to quantify thermogenic heat production across multiple adipose models, including adipocyte spheroids, freshly isolated adipocytes, and intact adipose tissue explants. Heat production scaled with spheroid size within a defined range and increased linearly with spheroid number per well, demonstrating the quantitative sensitivity of the calorimetric measurements. Pharmacological modulation of mitochondrial respiration in cultured primary beige adipocytes demonstrated that oxidative phosphorylation is a major driver of the calorimetric heat signal, including heat generation associated with mitochondrial proton leak. Freshly isolated adipocytes and intact adipose tissue exhibited depot-specific thermogenic activity and retained responsiveness to β-adrenergic stimulation ex vivo. Across adipose depots, intact tissue explants revealed unexpected differences in thermogenic heat production that were not fully reflected by thermogenic gene expression, highlighting divergence between molecular and functional readouts. Intact adipose tissue maintained measurable thermogenic heat production following extended ex vivo handling in nutrient-containing medium, such that tissues collected across a prolonged harvest window exhibited comparable calorimetric activity, enabling batch analysis of large experimental cohorts. Microcalorimetry further resolved regional differences in thermogenic heat production within the inguinal adipose depot following cold exposure. Together, these findings define key experimental considerations for applying isothermal microcalorimetry to adipose biology and demonstrate its utility for directly quantifying thermogenic metabolism in cells and intact tissues. Full article
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16 pages, 3769 KB  
Article
Terminalia bellirica Extract Attenuates Fat Accumulation Through Modulation of Obesity-Related Dysmetabolism in 3T3-L1 Adipocytes and High-Fat Diet-Induced Obese Mice
by Hyunyoung Choi, Yeonhwa Lee, Seong-Hoo Park, Jeongjin Park, Kun Hee Park, Kwang-Soo Baek, Jinhak Kim, Hyunmook Jung, Jaehwan Kim and Woojin Jun
Int. J. Mol. Sci. 2026, 27(4), 2014; https://doi.org/10.3390/ijms27042014 - 20 Feb 2026
Viewed by 624
Abstract
Terminalia bellirica extract (TBE) has long been utilized in Ayurvedic medicine across Indian and surrounding regions for diverse therapeutic applications. Despite its traditional prominence, systematic investigations addressing the anti-obesity efficacy and underlying mechanisms remain limited. In this study, we evaluated the anti-obesity potential [...] Read more.
Terminalia bellirica extract (TBE) has long been utilized in Ayurvedic medicine across Indian and surrounding regions for diverse therapeutic applications. Despite its traditional prominence, systematic investigations addressing the anti-obesity efficacy and underlying mechanisms remain limited. In this study, we evaluated the anti-obesity potential of TBE using both 3T3-L1 adipocyte and high-fat diet (HFD)-induced mice model. In vitro studies using 3T3-L1 adipocytes demonstrated that TBE significantly inhibited lipid accumulation and downregulated key genes involved in adipogenesis and lipogenesis, while upregulating genes promoted lipolysis and energy metabolism. To validate these cellular effects in a physiological context, mice were randomly assigned to six groups: normal control (NC), HFD-induced obese (C), HFD with metformin (100 mg/kg b.w., PC), and HFD with TBE at 50, 100, and 200 mg/kg b.w. Consistent with the in vitro findings, TBE supplementation significantly reduced body weight gain, adipose tissue mass, and adipocyte size in HFD-induced obese mice. Taken together, these results indicate that TBE exerts anti-obesity effects through modulation of adipose tissue metabolic pathways, highlighting its therapeutic potential for obesity management. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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12 pages, 558 KB  
Article
Assessing the Relationship Between Blubber Thickness and Adipocyte Size in Beluga Whales
by Jordan B. Stewart, Amanda M. Belanger and Cortney A. Watt
Animals 2026, 16(4), 650; https://doi.org/10.3390/ani16040650 - 18 Feb 2026
Viewed by 835
Abstract
Body condition, the relative amount of energy reserves in an individual, reflects nutritional status and overall health in marine mammals and can indicate the influence of stressors on individuals. Energy in marine mammals is primarily stored as lipids within adipocytes in blubber tissue, [...] Read more.
Body condition, the relative amount of energy reserves in an individual, reflects nutritional status and overall health in marine mammals and can indicate the influence of stressors on individuals. Energy in marine mammals is primarily stored as lipids within adipocytes in blubber tissue, making blubber thickness a common proxy for body condition. However, blubber also serves structural roles, complicating its use as a body condition indicator. Our objective was to assess the relationship between adipocyte size, a common measure of cetacean adiposity, and blubber thickness in beluga whales (Delphinapterus leucas). We used mixed-effect generalized linear models to test how sex and blubber layer influenced this relationship. We found a significant positive relationship between adipocyte size and blubber thickness in male but not female beluga whales, suggesting sex-specific differences in fat storage or mobilization. Blubber thickness may be maintained in female beluga whales during periods with low energy reserves, for example during gestation and lactation, to preserve buoyancy, insulation, and hydrodynamism, which may be especially important when supporting swimming calves. Continuing to develop methods to assess beluga whale health will further our understanding of the impact of current and future stressors on beluga whale populations. Full article
(This article belongs to the Section Mammals)
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16 pages, 3349 KB  
Article
A Combination of Amaranth Protein Hydrolysate and Korean Mint Extract Ameliorates Cisplatin-Induced Nephrotoxicity and Cachexia in CT26 Tumor-Bearing BALB/c Mice
by Junhee Lee, Yeeun Kim, Mi-Bo Kim, Ju Hyun Park, Daedong Kim, Dong-Woo Lee and Jae-Kwan Hwang
Nutrients 2026, 18(4), 665; https://doi.org/10.3390/nu18040665 - 18 Feb 2026
Viewed by 716
Abstract
Background/Objectives: Cancer cachexia involves progressive skeletal muscle and adipose tissue loss, which is further aggravated by cisplatin chemotherapy via increased systemic inflammation, tissue catabolism, and renal toxicity. The present study aimed to evaluate whether a combination of amaranth protein hydrolysate and Agastache rugosa [...] Read more.
Background/Objectives: Cancer cachexia involves progressive skeletal muscle and adipose tissue loss, which is further aggravated by cisplatin chemotherapy via increased systemic inflammation, tissue catabolism, and renal toxicity. The present study aimed to evaluate whether a combination of amaranth protein hydrolysate and Agastache rugosa extract (AKE) could attenuate cisplatin-associated cachexia and nephrotoxicity in CT26 tumor-bearing mice. Methods: Cancer cachexia was induced by subcutaneous CT26 cell inoculation in 6-week-old male BALB/c mice, followed by a 7-day tumor establishment period. Cisplatin was then administered intraperitoneally, and AKE (125 or 250 mg/kg/day) was given daily by oral gavage for 14 days. Results: AKE administration significantly alleviated cisplatin-induced body weight loss and systemic inflammation, accompanied by preservation of skeletal muscle and adipose tissue mass, as well as increased myofiber cross-sectional area and adipocyte size. AKE markedly reduced serum inflammatory cytokines, blood urea nitrogen, and creatinine levels, indicating protection against cisplatin-induced renal injury. Mechanistically, AKE suppressed renal apoptosis through inhibition of mitogen-activated protein kinase signaling. In skeletal muscle, AKE attenuated muscle atrophy by modulating protein turnover pathways, including downregulation of muscle-specific ubiquitin ligases and restoration of Akt/mTOR and FoxO3a signaling. Furthermore, AKE mitigated adipose tissue wasting by suppressing AMP-activated protein kinase-dependent browning and restoring adipogenic signaling involved in lipid storage and differentiation. Conclusions: These findings demonstrate that AKE confers comprehensive protection against cisplatin-induced cachexia and nephrotoxicity by coordinately preserving muscle and adipose tissue and attenuating renal injury, suggesting its potential as a functional nutritional strategy to alleviate chemotherapy-associated tissue wasting. Full article
(This article belongs to the Special Issue Botanicals and Nutritional Approaches in Metabolic Disorders)
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21 pages, 506 KB  
Review
Women with Endometriosis: A Narrative Review of Adiposity and Metabolic Function from a Biopsychosocial and Intersectional Perspective
by Carmen M. Galvez-Sánchez, Julio A. Camacho-Ruiz, Ana M. Contreras-Merino and Rosa M. Limiñana-Gras
Women 2026, 6(1), 12; https://doi.org/10.3390/women6010012 - 2 Feb 2026
Viewed by 1456
Abstract
Endometriosis is a chronic inflammatory disorder affecting about 190 million women of reproductive age worldwide. It represents a major health challenge due to its broad impact on physical, reproductive, and psychological well-being and is clinically characterized by pelvic pain, menstrual irregularities, and infertility. [...] Read more.
Endometriosis is a chronic inflammatory disorder affecting about 190 million women of reproductive age worldwide. It represents a major health challenge due to its broad impact on physical, reproductive, and psychological well-being and is clinically characterized by pelvic pain, menstrual irregularities, and infertility. This narrative review synthesized current evidence on the relationship between adiposity, metabolic and inflammatory markers, and endometriosis from a biopsychosocial and intersectional perspective. A comprehensive search was conducted in PubMed, Scopus, and Web of Science for peer-reviewed studies published in English over the past decade.: Results pointed out that endometriosis significantly affects inflammatory activity within adipose tissue, especially in visceral adipose tissue. Studies also reported reduced adipocyte size and altered adipose tissue function. The endometriosis cytokine profile exhibited a pattern of systemic and tissue-specific inflammatory activation (i.e., elevated levels of interleukin-6 and monocyte chemoattractant protein-1). Sociodemographic factors (i.e., age, race/ethnicity, socioeconomic status, and educational level) also play a significant role in differences in symptomatology, disease course, and healthcare access. To sum up, endometriosis need to be considered as a multisystem condition related to metabolic, inflammatory, and psychosocial factors. It is necessary to adopt a biopsychosocial and intersectional perspective to improve diagnosis and support more equitable and personalized therapeutic approaches. Full article
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21 pages, 6543 KB  
Article
Transplantation of Soluble Epoxide Hydrolase Inhibitor-Treated Human Brown Adipocytes Promotes Adipose Tissue Activation in High-Fat-Diet-Fed Nude Mice
by Haoying Wu, Xinyun Xu, Jiangang Chen, Christophe Morisseau, Bruce D. Hammock, Yu-Hua Tseng and Ling Zhao
Int. J. Mol. Sci. 2026, 27(3), 1440; https://doi.org/10.3390/ijms27031440 - 31 Jan 2026
Viewed by 748
Abstract
Brown adipose tissue (BAT) plays a key role in non-shivering thermogenesis and is a promising target for enhancing energy expenditure to combat obesity. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme that catalyzes the conversion of epoxy fatty acids into less active diols. [...] Read more.
Brown adipose tissue (BAT) plays a key role in non-shivering thermogenesis and is a promising target for enhancing energy expenditure to combat obesity. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme that catalyzes the conversion of epoxy fatty acids into less active diols. We have reported that local administration of the sEH inhibitor, t-TUCB, to the endogenous interscapular BAT (iBAT) of diet-induced obese mice decreased serum triglycerides and enhanced the expression of essential genes associated with lipid metabolism. Here, the effects of sEH inhibition by t-AUCB were assessed on human brown adipocyte (HuBr) differentiation and in nude mice transplanted with t-AUCB-treated HuBr. HuBr cells were differentiated with t-AUCB (1–10 µM) or the vehicle (0.1% DMSO). HuBr differentiated with t-AUCB at 5 μM (AUCB 5) or DMSO was mixed with matrix gel and transplanted into the nude mice. The mice were then fed a high-fat diet for eight weeks. The mice receiving AUCB 5-treated HuBr exhibited markedly reduced lipid accumulation in the iBAT compared with DMSO or matrix-only controls, along with increased protein expression of thermogenic PGC1α and UCP1, fatty acid transporter CD36, and CPT1A in the iBAT, while the NFκB inflammatory pathways were suppressed in both the AUCB 5 and DMSO groups. Moreover, the PGC1α and CPT1A protein levels were elevated, and the adipocyte sizes were decreased in the epididymal white adipose tissue of the AUCB 5 group. Our findings indicate that the transplantation of HuBr treated with AUCB 5 may stimulate thermogenesis, enhance lipid metabolism, and reduce inflammation in iBAT. Full article
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24 pages, 7205 KB  
Article
Influence of Donor Age, Donor Body Mass Index, and Harvesting Site on Cell Preparations from Human Adipose Tissue
by Olga Hahn, Philipp-Kjell Ficht, Wendy Bergmann-Ewert, Juliane Meyer, Anne Wolff and Kirsten Peters
Int. J. Mol. Sci. 2026, 27(3), 1351; https://doi.org/10.3390/ijms27031351 - 29 Jan 2026
Viewed by 693
Abstract
Adipose tissue includes various cell types beyond the typical adipocytes. The stromal vascular fraction (SVF) contains mesenchymal stem cells (MSCs), pericytes, and endothelial cells, which can be isolated from adipose tissue by mechanical and enzymatic methods. The composition of the SVF is heterogeneous, [...] Read more.
Adipose tissue includes various cell types beyond the typical adipocytes. The stromal vascular fraction (SVF) contains mesenchymal stem cells (MSCs), pericytes, and endothelial cells, which can be isolated from adipose tissue by mechanical and enzymatic methods. The composition of the SVF is heterogeneous, and donor factors such as sex, age, body mass index (BMI), and harvesting site are associated with variations in cellular composition and viability. The expression of specific surface markers, which determine the immunophenotype of the cells, can also vary. In this study, we investigated the effects of donor age, BMI, and harvesting site on cell yield, viability, and size. Our results showed that BMI significantly influenced cell yield and size, with overweight and obese donors yielding more cells than normal-weight donors. Additionally, cells isolated from the adipose tissue of the thighs/legs were larger than those from other areas. Flow cytometry showed considerable variability in SVF composition among donors. These results emphasize that SVF donor characteristics have a significant impact on cell yield, viability, and cell size, with the immunophenotype being highly donor-dependent. Understanding these factors is crucial for optimizing cell yield and defining populations for therapeutic applications of SVF cells. Full article
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14 pages, 2008 KB  
Article
Pilot Investigation on the Metabolic Effects of Cimicifuga racemosa Extract Ze 450 and Voluntary Physical Activity in Female Rats
by Elisabeth Habersatter, Tihomir Kostov, Nele Laing, Jürgen Drewe, Georg Boonen, Veronika Butterweck and Patrick Rene Diel
Int. J. Mol. Sci. 2026, 27(2), 977; https://doi.org/10.3390/ijms27020977 - 19 Jan 2026
Cited by 1 | Viewed by 485
Abstract
Cimicifuga racemosa extracts, particularly the ethanolic extract Ze 450, are widely used to alleviate menopausal symptoms, such as hot flushes and excessive sweating. While their clinical efficacy is well established, the effects of these interventions on systemic energy metabolism remain unclear. This pilot [...] Read more.
Cimicifuga racemosa extracts, particularly the ethanolic extract Ze 450, are widely used to alleviate menopausal symptoms, such as hot flushes and excessive sweating. While their clinical efficacy is well established, the effects of these interventions on systemic energy metabolism remain unclear. This pilot study investigated the impact of Ze 450 on body composition, metabolic markers, and voluntary physical activity in non-ovariectomized female Wistar rats. Animals (N = 36) received Ze 450 at either 30 mg/kg or 130 mg/kg body weight, with or without access to voluntary wheel running over four weeks. Neither treatment influenced body weight gain or final body weight, indicating normal growth across all groups. Post-mortem analyses included visceral fat mass, serum cholesterol, and leptin levels. Both Ze 450 and running reduced visceral fat mass, adipocyte size, and circulating leptin levels, suggesting that they share overlapping mechanisms. Serum cholesterol was significantly lowered by running but remained unaffected by Ze 450, while liver weight and alanine aminotransferase activity were unchanged, confirming hepatic safety. Collectively, Ze 450 improved key metabolic parameters related to adiposity and appetite without affecting hepatic integrity, highlighting its potential as a safe, non-hormonal metabolic modulator complementary to physical activity. Full article
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32 pages, 7080 KB  
Article
Enhanced Effects of Complex Tea Extract and the Postbiotic BPL1® HT on Ameliorating the Cardiometabolic Alterations Associated with Metabolic Syndrome in Mice
by Mario de la Fuente-Muñoz, Marta Román-Carmena, Sara Amor, Daniel González-Hedström, Verónica Martinez-Rios, Sonia Guilera-Bermell, Francisco Canet, Araceli Lamelas, Ángel Luis García-Villalón, Patricia Martorell, Antonio M. Inarejos-García and Miriam Granado
Int. J. Mol. Sci. 2026, 27(2), 680; https://doi.org/10.3390/ijms27020680 - 9 Jan 2026
Viewed by 840
Abstract
Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of type 2 diabetes and cardiovascular diseases. This study investigates the potential complementary effects of the standardized green and black ADM [...] Read more.
Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of type 2 diabetes and cardiovascular diseases. This study investigates the potential complementary effects of the standardized green and black ADM ComplexTea Extract (CTE) and the heat-treated postbiotic (BPL1® HT) on the cardiometabolic alterations associated with MetS in a murine model. C57BL/6J mice were fed a high-fat/high-sucrose (HFHS) diet and treated with CTE, BPL1® HT, or their combination for 20 weeks. Metabolic, inflammatory, oxidative, vascular parameters, and fecal microbiota composition were assessed. Both CTE and BPL1® HT individually attenuated weight gain, organ hypertrophy, insulin resistance, and inflammation. However, their combined administration exerted synergistic effects, fully normalizing body weight, adipocyte size, lipid profiles, HOMA-IR index, and insulin sensitivity to levels comparable to lean controls. Co-treatment also restored PI3K/Akt signaling in liver and muscle, reduced hepatic steatosis, and normalized the expression of inflammatory and oxidative stress markers across multiple tissues. Furthermore, vascular function was significantly improved, with enhanced endothelium-dependent relaxation and reduced vasoconstrictor responses, particularly to angiotensin II. CTE, BPL1®HT, and the blend prevented bacterial richness reduction caused by HFHS; the blend achieved higher bacterial richness than mice in Chow diet. Additionally, the blend prevented the increase in Flintibacter butyricus, which is associated with MetS clinical parameters, and showed a tendency to increase the abundance of Bifidobacterium. These findings suggest that the combination of CTE and BPL1® HT offers a potential nutritional strategy to counteract the metabolic and cardiovascular complications of MetS through complementary mechanisms involving improved insulin signaling, reduced inflammation and oxidative stress, enhanced vascular function, and modulation of gut microbiota. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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15 pages, 2719 KB  
Article
KBN2202 Suppresses Gonadal White Adipose Tissue Expansion in Female Mice Fed a High-Fat Diet
by Moonhang Kim, Jeong-Hyeon Heo, Seok Hwan Chang, Sun-Young Lee, Jihun Kim, Moon-Geun Shin, Jong Sung Kim, Mi Ran Choi and Sang-Rae Lee
Int. J. Mol. Sci. 2026, 27(2), 627; https://doi.org/10.3390/ijms27020627 - 8 Jan 2026
Viewed by 973
Abstract
Obesity treatments increasingly target multiple pathways beyond appetite suppression. We evaluated KBN2202, a salicylate-derived small molecule, in a high-fat diet (60% kcal from fat) mouse model using female and male C57BL/6J mice treated for 8 weeks with oral KBN2202 (20 mg/kg/day) or a [...] Read more.
Obesity treatments increasingly target multiple pathways beyond appetite suppression. We evaluated KBN2202, a salicylate-derived small molecule, in a high-fat diet (60% kcal from fat) mouse model using female and male C57BL/6J mice treated for 8 weeks with oral KBN2202 (20 mg/kg/day) or a matched-volume vehicle (1% DMSO/PBS). Body weight was recorded weekly, and food intake was measured daily; serum hormones and cytokines, adipose tissue histology, and open-field behavior were assessed at the end of the study. Under our experimental conditions, HFD increased body weight and gonadal white adipose tissue (gWAT)/brown adipose tissue (BAT) mass in females, whereas males showed only modest HFD-associated weight gain and did not develop a clear obesity phenotype. KBN2202 significantly reduced peri-ovarian gWAT mass and adipocyte size without altering overall body weight. In females, circulating glucagon-like peptide-1 (GLP-1) increased, uncoupling protein 1 (UCP1) in gWAT showed a non-significant upward trend, and serum TNF-α was selectively decreased, while MCP-1 and IL-1β were unchanged. Locomotor activity was unaltered, and anxiety-like behavior was reduced. Male mice did not show comparable adipose effects. These findings indicate depot-specific, peripheral modulation of adipose remodeling, hormonal balance, and inflammatory tone by KBN2202, supporting its further investigation as an adipose-targeted metabolic modulator complementary to incretin-based therapies. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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18 pages, 2662 KB  
Article
Anti-Obesity and Diuretic Effects of Immature Watermelon Rind Extract in HFD-Induced Obese Mice
by Yun-seong Lee, Ji yong Kim, Sunju So and Bo-Young Lee
Nutrients 2026, 18(1), 128; https://doi.org/10.3390/nu18010128 - 31 Dec 2025
Viewed by 1236
Abstract
Background/Objectives: Immature watermelon (WM) rind contains higher levels of citrulline and potassium than mature fruit and may exert diuretic and metabolic benefits. This study aimed to evaluate the anti-obesity and diuretic effects of WM and salt-treated watermelon rind extract (WMS) in high-fat diet [...] Read more.
Background/Objectives: Immature watermelon (WM) rind contains higher levels of citrulline and potassium than mature fruit and may exert diuretic and metabolic benefits. This study aimed to evaluate the anti-obesity and diuretic effects of WM and salt-treated watermelon rind extract (WMS) in high-fat diet (HFD)-induced obese mice, focusing on changes in lipid metabolism, sodium handling, and tissue-level alterations. Methods: Citrulline concentrations in WM and WMS were quantified using high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Four-week-old male C57BL/6 mice were fed an HFD for 6 weeks and subsequently administered WM (380 mg/kg) or WMS (380 mg/kg) orally for an additional 6 weeks. Body weight, food intake, organ and fat-pad weights, serum biochemical markers, and sodium (Na+) levels were measured. Histopathological analyses of liver and epididymal adipose tissue were performed to assess non-alcoholic steatohepatitis (NASH) scores and adipocyte morphology. Results: WM and WMS contained citrulline at levels substantially higher than those reported for mature watermelons. Both treatments significantly reduced body weight, liver weight, and epididymal fat mass compared with the HFD control. Serum total cholesterol and triglyceride levels were lowered in the WM- and WMS-treated groups. Serum Na+ concentrations increased by 43.2 ± 7.6% in WM-treated mice and 21.5 ± 6.6% in WMS-treated mice, suggesting enhanced sodium handling. Histological assessment revealed reduced NASH scores and smaller adipocyte sizes in both groups. These improvements are consistent with the known diuretic and metabolic actions of citrulline and potassium. Conclusions: WM and WMS exhibit significant anti-obesity and diuretic effects in HFD-induced obese mice. Their combined actions on sodium excretion, lipid metabolism, and adipose tissue remodeling suggest that immature watermelon rind extracts may serve as promising natural agents for preventing obesity and related metabolic dysfunction. Full article
(This article belongs to the Section Micronutrients and Human Health)
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21 pages, 1959 KB  
Article
Targeting Adipocyte Enhancer-Binding Protein 1 to Induce Microglial Phenotype Shift for Immunotherapy in Alzheimer’s Disease
by Eun-Ji Kim, Byeong-Hyeon Kim, Ye-Bin Mun, Minho Moon and Pyung-Hwan Kim
Int. J. Mol. Sci. 2026, 27(1), 296; https://doi.org/10.3390/ijms27010296 - 27 Dec 2025
Viewed by 997
Abstract
Neuroinflammation, a key contributor to neurodegenerative diseases, results from excessive microglial activation. Microglia that respond to pathogenic molecules switch to the M1 type and secrete various immune cytokines, which can cause neuronal damage. Therefore, our study focused on molecules that can enhance the [...] Read more.
Neuroinflammation, a key contributor to neurodegenerative diseases, results from excessive microglial activation. Microglia that respond to pathogenic molecules switch to the M1 type and secrete various immune cytokines, which can cause neuronal damage. Therefore, our study focused on molecules that can enhance the neuroprotective role of microglia and reduce neuronal damage. The adipocyte enhancer-binding protein 1 (AEBP1) gene is known for its role in regulating immune responses in macrophages. However, its role in neuroinflammation has not been fully explored. Therefore, we investigated the role of AEBP1 in microglial cells activated by lipopolysaccharide (LPS). First, we confirmed that AEBP1 is expressed in LPS-activated microglia and demonstrated that downregulation of AEBP1 using shRNA in activated microglia reduced the immune response via the nuclear factor-kappa-B (NFκB) pathway. These results promote a shift toward neuroprotective M2 microglia, thereby reducing neuronal damage. Next, we confirmed that the expression of AEBP1 was elevated in the brains of Alzheimer’s disease (AD) mice. Additionally, animal experiments to assess the therapeutic effects of AEBP1 showed that microglia gathered around amyloid beta (Aβ) and reduced its size. Taken together, our results provide the first evidence that AEBP1 can reduce inflammatory activity in microglia, suggesting its potential as a target molecule for immunotherapy. Full article
(This article belongs to the Special Issue Molecular Insights into Microglia in Neurological Diseases)
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17 pages, 3575 KB  
Article
Role of Exercise in Visceral Adipose Tissue Inflammation and Macrophage Polarization in Hypertensive Mice
by Venkata Polaki, Harshal Sawant, Brody Pinson, Cindy Zhu, Shuzhen Chen and Ji Chen Bihl
Int. J. Mol. Sci. 2026, 27(1), 251; https://doi.org/10.3390/ijms27010251 - 25 Dec 2025
Viewed by 835
Abstract
Macrophages accumulate in visceral adipose tissue (VAT) during hypertension and may contribute to hypertension-associated inflammation. Exercise has shown beneficial effects on hypertension; however, the exact mechanisms by which the activated immune cells lead to the protective effects remain unclear. Our study aimed to [...] Read more.
Macrophages accumulate in visceral adipose tissue (VAT) during hypertension and may contribute to hypertension-associated inflammation. Exercise has shown beneficial effects on hypertension; however, the exact mechanisms by which the activated immune cells lead to the protective effects remain unclear. Our study aimed to determine how exercise influences VAT inflammation by modulating the macrophage polarization in hypertensive mice. Renin transgenic (R+) mice were used as a hypertensive mouse model and subjected to exercise (8 weeks). The body weight and blood pressure were monitored, VAT morphology was assessed by H&E and Masson Trichrome staining, macrophage polarization was determined by immunostaining and flow cytometry, and macrophage phenotype-related proteins were analyzed within the VAT via Western Blots. Results showed that exercise reduced the adipocyte size and collagen content of VAT and increased cell infiltration in R+ mice. Immunostaining and flow cytometry data showed that the ratio of pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2) was increased in the VAT of R+ mice, while exercise corrected the macrophage polarization, which was consistent with protein level changes in VAT. Together, our data suggest that exercise improves vascular remodeling and VAT function (reduced adipocyte size, loss of collagen) by modulating VAT inflammation (polarization of macrophages) in hypertensive mice. Full article
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