Transient dietary intervention induces healthy adipose tissue expansion and metabolically healthy obesity in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE286421 | GEO | 2025/07/23
REPOSITORIES: GEO
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Project description:As obesity progresses, dynamic tissue remodeling of adipose tissue occurs over time, i.e., adipocyte hypertrophy, chronic inflammation, and interstitial fibrosis. Some obese individuals exhibit healthy adipose tissue expansion, characterized by modest inflammation and fibrosis despite adipocyte hypertrophy, resulting in “Metabolically Healthy Obesity (MHO)”. Our research has revealed that MHO can be induced by temporary weight loss during the development of obesity.
2025-07-23 | GSE286420 | GEO
Project description:Some people with obesity are resistant to the adverse metabolic effects of excess adiposity and are considered to have “metabolically healthy obesity” (MHO). However, the mechanisms responsible for MHO are not clear. We performed comprehensive cardiometabolic profiling in 20 adults with MHO (defined by features of normal insulin sensitivity), 20 age-, sex-, and BMI-matched adults with metabolically unhealthy obesity (MUO), and 15 adults who were metabolically healthy and lean (MHL). More than 120 variables were evaluated, including body composition, beta-cell function, 24-hour plasma metabolic profile, rates of de novo lipogenesis and cholesterol synthesis, plasma adipokine concentrations, oxidative stress, plasma lipoprotein profiles, cardiovascular structure/function, skeletal muscle bioactive lipids, and both adipose tissue and skeletal muscle transcriptomics. Using dimensionality reduction approaches, measures of insulinemia and skeletal muscle ceramides were the strongest discriminators of MHO and MUO status. These data clarify the characteristics associated with preserved metabolic health in response to obesity.
2024-03-06 | GSE244120 | GEO
Project description:Some people with obesity are resistant to the adverse metabolic effects of excess adiposity and are considered to have “metabolically healthy obesity” (MHO). However, the mechanisms responsible for MHO are not clear. We performed comprehensive cardiometabolic profiling in 20 adults with MHO (defined by features of normal insulin sensitivity), 20 age-, sex-, and BMI-matched adults with metabolically unhealthy obesity (MUO), and 15 adults who were metabolically healthy and lean (MHL). More than 120 variables were evaluated, including body composition, beta-cell function, 24-hour plasma metabolic profile, rates of de novo lipogenesis and cholesterol synthesis, plasma adipokine concentrations, oxidative stress, plasma lipoprotein profiles, cardiovascular structure/function, skeletal muscle bioactive lipids, and both adipose tissue and skeletal muscle transcriptomics. Using dimensionality reduction approaches, measures of insulinemia and skeletal muscle ceramides were the strongest discriminators of MHO and MUO status. These data clarify the characteristics associated with preserved metabolic health in response to obesity.
2024-03-06 | GSE244118 | GEO
Project description:People with obesity who do not have the metabolic syndrome or components of the metabolic syndrome have been characterized as having metabolically healthy obesity (MHO). However, the existence of MHO has been questioned because people with MHO are at greater risk of developing diabetes and fatal cardiovascular disease than people who are lean and healthy. A 25 year-old woman with rigorously defined MHO (based on normal oral glucose tolerance, insulin sensitivity (assessed by using the hyperinsulinemic-euglycemic clamp procedure), plasma triglyceride and HDL-cholesterol, intrahepatic triglyceride content and carotid intima-media thickness [CIMT]) was evaluated at baseline (BMI=37.7 kg/m2) and 5 years later, after gaining 30.8 kg (32%) in weight (BMI=49.6 kg/m2). The increase in weight was comprised of an 8.8 kg (20%) increase in FFM, 22.0 kg (42%) increase in total body fat, 8.1 kg (37%) increase in leg fat mass, 57% increase in subcutaneous abdominal fat and a 78% in intra-abdominal fat. Weight gain did not have adverse effects on fasting plasma glucose, oral glucose tolerance, beta-cell function, insulin sensitivity, plasma triglyceride, intrahepatic triglyceride content and CIMT. Adipose tissue expression of genes involved in extracellular matrix formation did not change. Adipose tissue expression of several inflammation-related genes increased by more than 30%, but was not associated with a corresponding increase in plasma cytokine concentrations, with the exception of an increase in plasma IL-6. The present case study demonstrates that some people with obesity are resistant to the adverse cardiometabolic effects of excess adiposity and marked weight gain.
2023-11-01 | GSE217154 | GEO
Project description:Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO).
2021-03-23 | GSE169290 | GEO
Project description:Not all obese individuals develop the usual comorbidities (i.e. hypertension, dyslipidemia, diabetes) despite the excess weight. We set out to investigate this metabolically healthy obesity (MHO) phenomenon utilizing a collection of monozygotic twins discordant for obesity. Adipose tissue samples were analyzed for diffences in their transcipt profile between groups of MHO and non-MHO twin pairs.
2013-10-16 | E-MTAB-1895 | biostudies-arrayexpress
Project description:Obesity and adipose tissues quality are important risk factors for the development of type 2 diabetes and metabolic syndrome; this risk is related to intrinsic differences in the behavior of adipocytes in different fat depots. We have shown that the liver fatty acid-binding protein null (LFABP-/-) mouse is a model of the ‘metabolically healthy obese’ (MHO) state. Here, we demonstrate that the LFABP-/- mouse is a novel model of hyperplastic subcutaneous adipose tissue (SAT). LFABP-/-mice fed a high-fat diet (HFD) for 12 weeks gained 27% more weight (BW, g: 43.6 LFABP-/- vs 34.4 WT, P<0.001, n=10) and their fat mass was almost double (Fat, g: 15.4 LFABP-/-vs8.3 WT, P<0.001, n=10) that of WT. Intriguingly, despite the substantial increase in mass, inguinal white adipose tissue (iWAT) adipocyte size was >4-fold smaller (46pL LFABP-/-vs222pL WT per cell, P<0.001, n=5) and adipocyte number was 5-fold higher (23.6 LFABP-/-vs4.7 WT x 106, P=0.001, n=5) in the iWAT of LFABP-/-compared to WT mice. Upon obesity development, Lfabp deletion results in transcriptomic differences that include large effects on cholesterol biosynthesis and extracellular matrix (ECM) remodeling, likely leading to tissue growth and a state of ‘adaptive fibrosis’ and ‘homeostatic adipogenesis’ for safe excess energy storage. Since LFABP is not expressed in adipose tissues, these results suggest that its ablation promotes interorgan signaling that may limit hypertrophy and drive hyperplasia in expansion of potentially metabolically beneficial SAT, contributing to the MHO phenotype of the LFABP-/-mouse.
2025-06-18 | GSE277001 | GEO
Project description:Obesity is a heterogeneous conditions comprising obese individuals with metabolic disorders (termed metabolically unhealthy obese; MUO) and obese individuals who are metabolically healthy (termed metabolically healthy obese; MHO). We used microarrays to examine differences in subcutaneous adipose tissue gene expression from lean healthy (LH), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) individuals. Subcutaneous adipose tissue samples from the periumbilical region were obtained under local anesthesia and after an overnight fast. 50-100 mg of adipose tissue was homogenized and total RNA was extracted after homogenisation in TRIzol reagent using a tissue homogenizer.
2014-11-14 | E-GEOD-55200 | biostudies-arrayexpress
Project description:Obesity is a heterogeneous conditions comprising obese individuals with metabolic disorders (termed metabolically unhealthy obese; MUO) and obese individuals who are metabolically healthy (termed metabolically healthy obese; MHO). We used microarrays to examine differences in subcutaneous adipose tissue gene expression from lean healthy (LH), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) individuals.
2014-11-14 | GSE55200 | GEO
Project description:Background/aims: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type‐2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO) opening the possibility that FGF21 is a cross‐talker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion. Methods/study design: In 20 morbidly obese donors of abdominal subcutaneous fat biopsies discordant for their whole‐body insulin sensitivity (hereby classified as MHO or MUHO subjects), serum FGF21 was quantified. The impact of chronic FGF21 treatment on differentiation, lipid accumulation, and adipokine release was assessed in isolated preadipocytes differentiated in vitro. Results: Serum FGF21 concentrations were more than two‐fold higher in MUHO as compared to 37 MHO subjects (457 ±378 vs. 211 ±123 pg/mL; p<0.05). FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p<0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, ‐15% and ‐40%, respectively; p<0.01 both), reduced adiponectin expression (‐20%; p<0.05), markedly reduced adiponectin release (‐60%; p<0.01), and substantially increased leptin (+60%; p<0.01) and interleukin‐6 (+50%; p<0.001) release. Interpretation/conclusions: The hepatokine FGF21 exerts weak lipogenic and anti‐adipogenic actions and marked adiponectin‐suppressive and leptin and interleukin‐6 release‐promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes. We analysed in vitro differentiated preadipocytes from 20 human donors treated with FGF21 or control cultures.
2015-05-19 | E-GEOD-67279 | biostudies-arrayexpress