Molecular effects of lifestyle interventions are typically studied in a single tissue. Here, we perform a secondary analysis on the sex-specific effects of the Growing Old TOgether trial (GOTO, trial registration number GOT NL3301 ( https://onderzoekmetmensen.nl/nl/trial/27183 ), NL-OMON27183 , primary outcomes have been previously reported in ref. 1), a moderate 13-week combined lifestyle intervention on the transcriptomes of postprandial blood, subcutaneous adipose tissue (SAT) and muscle tissue in healthy older adults, the overlap in effect between tissues and their relation to whole-body parameters of metabolic health. The GOTO intervention has virtually no effect on the postprandial blood transcriptome, while the SAT and muscle transcriptomes respond significantly. In SAT, pathways involved in HDL remodeling, O2/CO2 exchange and signaling are overrepresented, while in muscle, collagen and extracellular matrix pathways are significantly overexpressed. Additionally, we find that the effects of the SAT transcriptome closest associates with gains in metabolic health. Lastly, in males, we identify a shared variation between the transcriptomes of the three tissues. We conclude that the GOTO intervention has a significant effect on metabolic and muscle fibre pathways in the SAT and muscle transcriptome, respectively. Aligning the response in the three tissues revealed a blood transcriptome component which may act as an integrated health marker for metabolic intervention effects across tissues.

In humans, α-tocopherol (α-TOC) is mainly stored in adipose tissue, where it participates in preventing damages induced by inflammation and reactive oxygen species. Factors, including genetic ones, that explain adipose tissue α-TOC concentration remain poorly understood. This study, therefore, aimed to characterize the interindividual variability of adipose tissue α-TOC concentration in healthy individuals and to identify single nucleotide polymorphisms (SNPs) associated with it. The study used a randomized cross-over design with 42 healthy adult males. α-TOC concentration was measured in fasting plasma and periumbilical adipose tissue samples, both at fast and 8 h after consumption of three standard meals. Partial least squares (PLS) regression was performed to identify SNPs associated with the interindividual variability of adipose tissue α-TOC concentration. Adipose tissue α-TOC concentration was not associated with fasting plasma concentration (Pearson\'s r = 0.24, 95% CI: [-0.08, 0.51]). There was a high interindividual variability of adipose tissue α-TOC concentration (CV = 61%). A PLS regression model comprising 10 SNPs in five genes (PPARG, ABCA1, BUD13, CD36, and MGLL) explained 60% (adjusted R2) of the variability of this concentration. The interindividual variability of adipose tissue α-TOC concentration in humans is due, at least partly, to SNPs in genes involved in α-TOC and triglyceride metabolism.

Adipose tissue is a dynamic regulatory organ that has profound effects on the overall health of patients. Unfortunately, inconsistencies in human adipose tissues are extensive and multifactorial, including large variability in cellular sizes, lipid content, inflammation, extracellular matrix components, mechanics, and cytokines secreted. Given the high human variability, and since much of what is known about adipose tissue is from animal models, we sought to establish correlations and patterns between biological, mechanical, and epidemiological properties of human adipose tissues. To do this, twenty-six independent variables were cataloged for twenty patients, which included patient demographics and factors that drive health, obesity, and fibrosis. A factorial analysis for mixed data (FAMD) was used to analyze patterns in the dataset (with BMI > 25), and a correlation matrix was used to identify interactions between quantitative variables. Vascular endothelial growth factor A (VEGFA) and actin alpha 2, smooth muscle (ACTA2) gene expression were the highest loadings in the first two dimensions of the FAMD. The number of adipocytes was also a key driver of patient-related differences, where a decrease in the density of adipocytes was associated with aging. Aging was also correlated with a decrease in overall lipid percentage of subcutaneous tissue, with lipid deposition being favored extracellularly, an increase in transforming growth factor-β1 (TGFβ1), and an increase in M1 macrophage polarization. An important finding was that self-identified race contributed to variance between patients in this study, where Black patients had significantly lower gene expression levels of TGFβ1 and ACTA2. This finding supports the urgent need to account for patient ancestry in biomedical research to develop better therapeutic strategies for all patients. Another important finding was that TGFβ induced factor homeobox 1 (TGIF1), an understudied signaling molecule, which is highly correlated with leptin signaling, was correlated with metabolic inflammation. Furthermore, this study draws attention to what we define as \"extracellular lipid droplets\", which were consistently found in collagen-rich regions of the obese adipose tissues evaluated here. Reduced levels of TGIF1 were correlated with higher numbers of extracellular lipid droplets and an inability to suppress fibrotic changes in adipose tissue. Finally, this study indicated that M1 and M2 macrophage markers were correlated with each other and leptin in patients with a BMI > 25. This finding supports growing evidence that macrophage polarization in obesity involves a complex, interconnecting network system rather than a full switch in activation patterns from M2 to M1 with increasing body mass. Overall, this study reinforces key findings in animal studies and identifies important areas for future research, where human and animal studies are divergent. Understanding key drivers of human patient variability is required to unravel the complex metabolic health of unique patients.

BACKGROUND: Temporal concavities result from reduced subcutaneous fat and bone structure variations, impacting facial aesthetics. Filling treatments, including autologous fat grafts, synthetic fillers, and biological materials, are used for enhancement. Autologous fat grafting is promising but limited by unpredictable fat absorption and nonstandardized procedures. This study aims to assess the clinical effectiveness of mechanical micronized fat in combination with autologous granular fat grafting for lipofilling in the correction of temporal deformities.
METHODS: Patients (n = 37, mean age = 37.48) with temporal concavity caused by aging and Inherently inadequate capacity were enrolled and divided into control group (n = 10) and study group (n = 9) according to different fat grafts. Control group received pure autologous granular fat, with an average volume of approximately 19.30 mL. In contrast, the study group used mechanical micronized fat along with autologous granular fat co-injection through an 18G needle with an average injection volume of about 18.89 mL. All autologous fat collected from patients\' abdominal and thighs. Information, including postoperative clinical efficacy scored by various plastic surgeons for the comparison of preoperative and postoperative photos of patients, patient satisfaction, and complications between the two groups, was documented. Additionally, changes in patients\' quality of life were evaluated using the FACE-Q scale.
RESULTS: Six months after surgery, the efficacy of temporal filling in the study group (6.69 ± 0.64) was higher than the control group (6.37 ± 0.67) (P = 0.0048). The patient satisfaction was more prominent in the study group (6.28 ± 0.87) than in the control group (5.80 ± 0.71) (P = 0.0449). Differences between above two observation indicators were statistically significant (P < 0.05). The FACE-Q scale items, which assess psychological health, social functioning, and early life impact, showed higher scores in the study group both before the surgery (psychological health: 59.22 ± 3.53, social functioning: 64.75 ± 3.15) and 6 months after the surgery (psychological health: 69.44 ± 4.50, social functioning: 75.33 ± 3.81, early life impact: 74.21 ± 0.70) (P > 0.05). Notably, only one micronodule formation was detected among all patients.
CONCLUSIONS: Mechanical micronized fat combined with autologous granular fat improve the clinical effect of treating concavity in temporal region, which is worthy of further promotion and application.

UNASSIGNED: The purpose of this study was to assess if subcutaneous fat (SCF) or BMI is a predictor of surgical complications and patient reported outcomes in patients undergoing robotic-assisted total hip arthroplasty (THA).
UNASSIGNED: Patients who underwent robotic-assisted primary THAs at one institution between 2018 and 2020 were included in this retrospective cohort study. Prior to surgery, computed tomography (CT) was used to measure SCF in the posterolateral quadrant of the hip. SCF was measured 3 centimeters (cm) proximal to the greater trochanter (PGT) and 3 cm inferior to the distal tip of the greater trochanter (DGT).Measurements were normalized to the size of the patient\'s bony anatomy by dividing the subcutaneous fat area measurement by the transverse diameter of the femur 10 cm inferior to the tip of the greater trochanter. Patients were divided into quintiles determined by SCF distribution around the mean (groups 1-5) and BMI (BMI<25, BMI 25-29.9, BMI 30-34.9, BMI 35-39.9, and >40). Ninety day outcomes and PROMIS (Patient Reported Outcome Measures Information System) scores were acquired from the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) database preoperatively, at 14-112 days post-operative and at the latest follow up.
UNASSIGNED: There were 175 patients identified with a mean age of 63.83 years (range 27-89) and a mean BMI of 30.73kg/m2 (range 18.2-48.4). Interclass correlation coefficient was greater than 0.9 in all PGT, DGT, and GT measurements. Analysis of Variance (ANOVA) found there was a significantly shorter time from incision to closure in quintiles 1 and 3 when compared to the SCF quintile 5 (p<0.05) and that there was a significantly shorter time from incision to closure in BMI categories 1, 2, and 3 when compared to BMI category 5 (BMI > 40). There were no differences between SCF and BMI as predictive of length of stay, transfusion status, infection, or PROMIS scores.
UNASSIGNED: It can be concluded that hip SCF on axial CT images can reliably measure SCF and is predictive of time from incision to closure, but it does not show a significant difference in predicting the length of stay, infection, or PROMIS scores when compared to BMI.

OBJECTIVE: Adipose tissue has been associated with knee osteoarthritis (KOA) pathogenesis, but the longitudinal changes in adipose tissue with KOA progression have not been carefully evaluated. This study aimed to determine if longitudinal changes of systemic and local adipose tissue is associated with radiographic progression of KOA.
METHODS: This case-control study used data from the Osteoarthritis Initiative (OAI) and included 315 cases (all the right knees with a minimum of Kellgren-Lawrence score (KL) of 0 and an increase of ≥ 1 KL from baseline to 48 months) and 315 controls matched by age, sex, race, and baseline KL. Cross sectional area of IPFP (IPFP CSA) and subcutaneous adipose tissue around the distal thigh (SCATthigh) were measured using MRI images at baseline and 24 months. Conditional logistic regression models were fitted to estimate associations of obesity markers, IPFP CSA, and SCATthigh with radiographic KOA progression. Mediation analysis was used to assess whether IPFP CSA or SCATthigh mediates the relationships between baseline BMI and radiographic KOA progression.
RESULTS: 24-month changes of IPFP CSA (ΔIPFP CSA) and SCATthigh (ΔSCATthigh) were significantly greater in cases compared to controls, whereas Δ BMI and Δ abdominal circumference were similar in both groups during follow-up. Adjusted ORs for radiographic KOA progression were 9.299, 95% CI (5.357-16.141) per 1 SD increase of Δ IPFP CSA and 1.646, 95% CI (1.288-2.103) per 1 SD increase of Δ SCATthigh. ΔIPFP CSA mediated the association between baseline BMI and radiographic KOA progression (87%).
CONCLUSIONS: Subjects with radiographic progression of KOA, had significant increases in IPFP CSA and subcutaneous adipose tissue while BMI and abdominal circumference remained stable. Additional studies are needed to confirm these associations.

Decreased medial cheek fat volume during aging leads to loss of a youthful facial shape. Increasing facial volume by methods such as adipose-derived stem cell (ASC) injection can produce facial rejuvenation. High-intensity focused ultrasound (HIFU) can increase adipogenesis in subcutaneous fat by modulating cilia on ASCs, which is accompanied by increased HSP70 and decreased NF-κB expression. Thus, we evaluated the effect of HIFU on increasing facial adipogenesis in swine (n = 2) via modulation of ASC cilia. Expression of CD166, an ASC marker, differed by subcutaneous adipose tissue location. CD166 expression in the zygomatic arch (ZA) was significantly higher than that in the subcutaneous adipose tissue in the mandible or lateral temporal areas. HIFU was applied only on the right side of the face, which was compared with the left side, where HIFU was not applied, as a control. HIFU produced a significant increase in HSP70 expression, decreased expression of NF-κB and a cilia disassembly factor (AURKA), and increased expression of a cilia increasing factor (ARL13B) and PPARG and CEBPA, which are the main regulators of adipogenesis. All of these changes were most prominent at the ZA. Facial adipose tissue thickness was also increased by HIFU. Adipose tissue volume, evaluated by magnetic resonance imaging, was increased by HIFU, most prominently in the ZA. In conclusion, HIFU increased ASC marker expression, accompanied by increased HSP70 and decreased NF-κB expression. Additionally, changes in cilia disassembly and length and expression of adipogenesis were observed. These results suggest that HIFU could be used to increase facial volume by modulating adipogenesis.

Substituting traditional protein feed with palm kernel meal (PKM) in the diet of Tibetan sheep can be a cost-effective feeding strategy. To determine the impact of PKM on flavor development in different adipose tissues of Tibetan sheep, subjects were fed with 15% and 18% of PKM, while the control group received no PKM. The fatty acids and volatile compounds in the samples were then analyzed by GC-MS and HS-GC-IMS. Adding PKM to the diet significantly increased the C12:0, C14:0, C16:0 and C18:1N9 content in adipose tissues compared with the control, and most of these were associated with flavor formation (p < 0.05). The flavor compounds in the adipose tissues predominantly consisted of alcohols, ketones, acids and aldehydes. In particular, including PKM in the diet increased the proportion of ketones but decreased the proportion of alcohols, acids and aldehydes in subcutaneous and tail fat. Specifically, the proportion of acetone, acetoin monomer, 2,3-butanedione, 2-butanone monomer, 2-methyl-2-propanol, 2-methyl-2-propanol and methyl acetate increased significantly in the subcutaneous and tail fat (p < 0.05), while that of ethanol, 1-propanol monomer, butanol monomer, acetic acid monomer and acetic acid monomer decreased. Intermuscular fat exhibited variable results, mainly because the addition of PKM resulted in higher proportions of alcohols, including ethanol, 1-propanol and butanol monomer, especially at 15% PKM. In summary, the addition of PKM improved the flavor of Tibetan sheep fat and increased the amount of favorable volatile flavor compounds. This study can serve as reference for understanding the effects of dietary PKM on the adipose tissue flavor profile of Tibetan sheep.

OBJECTIVE: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex.
METHODS: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis.
RESULTS: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females.
CONCLUSIONS: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival.

We aimed to examine the effect of age of obesity onset, sex, and their interaction on abdominal and femoral subcutaneous adipose tissue (SAT) morphology (degree of adipocyte hyperplasia or hypertrophy).
In this cross-sectional study, we isolated adipocytes via collagenase digestion from abdominal and femoral SAT biopsies taken from male and female adults with childhood-onset obesity (CO; n = 8 males, n = 16 females) or adult-onset obesity (AO; n = 8 males, n = 13 females). Regional body composition was measured with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan. Mean adipocyte size was measured in abdominal and femoral SAT and was used to quantify morphology in android and gynoid subcutaneous fat, respectively.
Abdominal SAT morphology was more hyperplastic in females with CO than females with AO (p = 0.004) but did not differ between males with CO and males with AO (p = 0.996). Conversely, femoral SAT morphology was more hypertrophic in males and females with CO than those with AO.
Age of obesity onset appears to affect SAT morphology differently in the abdominal and femoral regions of male and female adults. Our findings challenge the notion that SAT is uniformly hyperplastic in CO and hypertrophic in AO.