OBJECTIVE: With the growing demand for more effective fat reduction techniques, a combination of synchronized radiofrequency (RF) and HIFEM has been introduced. Preceding studies evidenced the ability of RF+HIFEM to maintain the fat tissue temperature at the levels necessary for adipocyte apoptosis while documenting the induced changes to the fat tissue during the several weeks after the treatment. This study aims to demonstrate the induction of apoptosis by RF+HIFEM technology in the early stages through the assessment of caspase-3 protein, one of the apoptosis-executing proteases.
METHODS: In this two-arm, single-center, randomized trial, nine human subjects were enrolled and assigned into two groups, either the active group (N = 6) treated with both RF+HIFEM set at the highest tolerated levels or the sham group (N = 3) treated with 5% of the maximum RF+HIFEM power, serving as a control. All patients were scheduled to undergo one treatment visit of the abdominal area, two follow-up visits at 8 and 24 h, and one safety visit 7 days after the treatment. A punch biopsy (5 mm in diameter, approximately 10 mm in depth) was obtained from the abdominal area at the baseline and consecutive follow-up visits. Samples were fixed, and cut into 5 μm thick slices, and immunohistochemical staining was used to visualize the Caspase-3, revealing the adipocyte nuclei where apoptosis processes are in progress.
RESULTS: Documented findings suggest that the temperature threshold of 43-45°C is required to initiate fat apoptosis and consequent reduction in adipocyte number was achieved during the combined treatment with RF+HIFEM. The active group showed an elevated ratio of positively stained nuclei versus all adipocyte nuclei found on the evaluated slices-referred to as the apoptotic index (AI). The AI significantly (p < 0.001) increased at both 8 h (47.01 ± 10.56%) and 24 h (43.58 ± 6.35%) posttreatment. The Sham group showed no significant change in the AI (p > 0.05). No adverse events or side effects related to the treatments were observed.
CONCLUSIONS: This study supports previously published evidence on fat reduction after RF+HIFEM treatment, documenting the safe initiation of adipocyte programmed cell death posttreatment.

CBL-514 is a novel injectable drug that may be safe and efficacious for localized abdominal subcutaneous fat reduction.
The aim of this study was to assess the safety and efficacy of CBL-514 in reducing abdominal subcutaneous fat volume and thickness.
This Phase IIa, open-label, random allocation study consisted of a 6-week treatment period and follow-up at 4 and 8 weeks following the last treatment. Participants were randomly allocated to receive 1.2 mg/cm2 (180 mg), 1.6 mg/cm2 (240 mg), or 2.0 mg/cm2 (300 mg) of CBL-514 with up to 4 treatments, each comprising 60 injections into the abdominal adipose layer. Changes in abdominal subcutaneous fat were assessed by ultrasound at follow-up visits. Treatment-emergent adverse events were recorded.
Higher doses of CBL-514 (unit dose, 2.0 and 1.6 mg/cm2) significantly improved the absolute and percentage reduction in abdominal fat volume (P < 0.00001) and thickness (P < 0.0001) compared with baseline. Although the COVID-19 pandemic halted some participant recruitment and follow-ups, analysis was unaffected, even after sample size limitations.
CBL-514 injection at multiple doses up to 300 mg with a unit dose of 2.0 mg/cm2 is safe, well-tolerated, and reduced abdominal fat volume and thickness by inducing adipocyte apoptosis. Although other procedures exist to treat abdominal fat, they have limitations and may cause complications. At a dose of 2.0 mg/cm2, CBL-514 safely and significantly reduced abdominal fat volume by 24.96%, making it a promising new treatment for routine, nonsurgical abdominal fat reduction in dermatologic clinics.

Higher levels of intra-abdominal adipose tissue (IAAT) comprising visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT), and liver fat are posited drivers of obesity-related chronic disease risk. Fast food is hypothesized to contribute to IAAT patterns.
We quantified levels of abdominal subcutaneous adipose tissue (SAT), IAAT, and odds of metabolic-associated fatty liver disease (MAFLD) in middle age according to average fast-food intake over the preceding 25 y.
We analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants underwent 6 clinical exams and measurements over 25 y with computed tomography-measured VAT, SAT, and IMAT (n = 3156), plus MAFLD defined by liver attenuation (≤40 Hounsfield units) and 1 metabolic abnormality at year 25 (2010, n = 3001, n cases = 302). We estimated means of VAT, SAT, IMAT, and liver attenuation at the year 25 exam according to categories of average fast-food intake over the previous 25 y adjusted for sociodemographic and lifestyle factors and logistic regression to estimate the odds ratio of MAFLD at year 25.
With higher average fast-food intake over 25 y (categorized as follows: never-1×/mo, >1×-3×/mo, 1-<2×/wk, 2-<3×/wk, ≥3×/wk), there were monotonic higher levels of VAT (98.5, 127.6, 134.5, 142.0, 145.5 cm3), P-trend < 0.0001, which were consistent across anthropometrically classified obesity categories. There was a similar pattern with liver fat. There were higher levels of IMAT and SAT with higher fast-food intake (P-trend = 0.003, 0.0002, respectively), with amounts leveling off at ≥2×/wk. In addition, compared with participants who ate fast food never-1×/mo, there were monotonic higher odds of having MAFLD at year 25 with higher average fast-food intake, with participants who ate fast food ≥3×/wk having an OR of MAFLD = 5.18 (95% CI: 2.87, 9.37).
There were monotonic higher levels of VAT, liver fat, and odds of having MAFLD in middle age according to higher average fast-food intake over the preceding 25 y.

The aim of this study was to examine whether nutrient intakes in childhood are associated with abdominal and hepatic fat depots later in adolescence.
Using data from 302 participants in the longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) study, energy partition and nutrient density models were constructed to examine associations of nutrient intakes in childhood (~10 years of age), assessed by food frequency questionnaire, with abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and hepatic fat in adolescence (~16 years of age).
In energy partition models (energy intake not held constant), total, monounsaturated, and polyunsaturated fat intakes in childhood were associated with higher SAT in adolescence (β [95% CI]: 8.5 [0.1-17.1], 25.1 [2.1-48.1], and 59.7 [16.1-103.3] mm2 per 100 kcal/d), higher starch intake was associated with log-hepatic fat (back-transformed β [95% CI]: 1.07 [1.01-1.15] per 100 kcal/d), and, in boys only, higher animal protein intake was associated with VAT (β [95% CI]: 5.3 [0.3-10.3] mm2 per 100 kcal/d). Most associations were unchanged when adjusted for energy intake in nutrient density models.
Childhood nutrient intakes were differentially associated with adolescent body fats; specifically, unsaturated fat intake predicted abdominal SAT, animal protein intake predicted VAT, and starch intake predicted hepatic fat. These nutrient intakes may, therefore, be targets for intervention studies aiming to modify adolescent body fat distribution.

The study evaluated the association between nutrient patterns with body fat and regional adiposity in middle-aged black South African (SA) men and women and determined if this differed by sex. Body fat and regional adiposity (dual-energy x-ray absorptiometry), and dietary intake (7-day quantified food frequency questionnaire) were measured in black SA men (n = 414) and women (n = 346). Using principal component analysis, nutrient patterns were computed from 25 nutrients in the combined sample. Four nutrient patterns were extracted, explaining 67% of the variance in nutrient intake. Animal and fat, as well as the vitamin C, sugar, and potassium driven patterns, were positively associated with total adiposity. In contrast, the retinol and vitamin B12 pattern was associated with the centralisation of fat. Notably, the strength of the association between the animal-driven nutrient pattern and BMI was greater in men (1.14 kg/m2, 95% CI (0.63-1.66)) than in women (0.81 kg/m2, 95% CI (0.25-1.36)) (Pint = 0.017). In contrast, the plant-driven pattern was associated with higher abdominal subcutaneous adipose tissue (SAT) in women (44 cm2, 95% CI (22-67)) but not men (Pint = 1.54 × 10-4). These differences suggest that although men and women have similar nutrient patterns, their associations with the whole body and regional body fat are different.

BACKGROUND: It was reported that steroid-related gene expressions in the adipose tissue (AT) of women differ between women affected with polycystic ovary syndrome (PCOS) and non-PCOS. Although association between PCOS in mother and offspring\'s health is a crucial issue, there are few studies focusing on AT of pregnant women suffering from PCOS. Our objectives were to determine the differences between mRNA expression levels of key steroid-converting enzymes in abdominal subcutaneous AT of pregnant women afflicted with PCOS and non-PCOS.
METHODS: Twelve pregnant women with PCOS (case) and thirty six non-PCOS pregnant women (control) (1:3 ratio; age- and BMI-matched) undergoing cesarean section were enrolled for the present study. Expressions of fifteen genes related to steriodogenesis in abdominal subcutaneous AT were investigated using quantitative real-time PCR.
RESULTS: No significant differences were detected with respect to age, BMI (prior pregnancy and at delivery day), gestational period and parity among pregnant women with PCOS and non-PCOS. Most of the sex steroid-converting genes except 17β-Hydroxysteroid dehydrogenases2 (17BHSD2), were highly expressed on the day of delivery in subcutaneous AT. Women with PCOS showed significantly higher mRNA levels of steroidgenic acute regulator (STAR; P < 0.001), cytochrome P450 monooxygenase (CYP11A1; P < 0.05), 17α-hydroxylase (CYP17A1; P < 0.05), and 11β-Hydroxysteroid dehydrogenase (11BHSD1 and 11BHSD2; P < 0.05). The expression of steroid 21-hydroxylase (CYP21) in non-PCOS was fourfold higher than those of women with PCOS (P < 0.001). There were no significant differences between relative expression of aromatase cytochrome P450 (CYP19A1), 3β-hydroxysteroid dehydrogenase (3BHSD1 and 3BHSD2), and 17BHSD family (1, 3, 5, 7, and 12) between the two groups.
CONCLUSIONS: The expression levels of genes related to sex steroids metabolism were similar to age-matched and BMI- matched pregnant non-PCOS and pregnant women with PCOS at delivery day. However, the alterations in gene expressions involved in glucocorticoids and mineralocorticoids metabolism were shown. It is necessary to point out that further studies regarding functional activity are required. More attention should be given to AT of pregnant women with PCOS that was previously ignored.

Adipose tissue (AT) senescence is associated with AT dysfunction in rodents, but little is known about human AT senescence. The study goal was to define the distribution of senescent cells in two subcutaneous depots and understand relationships with adiposity and inflammation.
Sixty-three volunteers (48 females) underwent abdominal and femoral subcutaneous fat biopsies. Fat cell size, senescent cells using senescence-associated β-galactosidase staining per 100 nucleated cells (percentage), and mRNA expression of four cytokines were measured.
There was a larger proportion of senescent cells in femoral than abdominal subcutaneous AT (mean difference 1.6% [95% CI: 0.98%-2.3%], p < 0.001), and the percentage of femoral AT senescent cells was greater in women than men (median 3.9% vs. 2.1%, p < 0.01). There was a positive correlation between senescence and fat cell size in abdominal (rs  = 0.44, p < 0.001) and femoral (rs  = 0.35, p = 0.007) AT depots. Abdominal AT tumor necrosis factor alpha (rs  = 0.49, p < 0.01) and interleukin-1β (rs  = 0.44, p = 0.01) expression was positively correlated with abdominal, but not femoral, AT senescence.
In human subcutaneous AT, there are more senescent cells in femoral than abdominal depots; abdominal AT senescent cells are more associated with inflammatory signals than femoral AT senescent cells.

In addition to reducing subcutaneous fat for body contouring, some patients are interested in toning the underlying muscle layer.
This feasibility study evaluated the safety and efficacy of electromagnetic muscle stimulation (EMMS) alone, cryolipolysis alone, and cryolipolysis with EMMS for noninvasive contouring of abdomen.
Abdomens of 50 subjects were treated in a study with 3 cohorts: EMMS alone, Cryolipolysis alone, and Cryolipolysis + EMMS in combination. Electromagnetic muscle stimulation treatments were delivered in 4 sessions over 2 weeks. Cryolipolysis treatments were delivered in one session. Combination treatments consisted of one cryolipolysis and 4 EMMS visits. Efficacy was assessed by independent physician Global Aesthetic Improvement Scale (GAIS), circumferential measurement, Subject GAIS (SGAIS), and Body Satisfaction Questionnaire (BSQ).
Safety was demonstrated for all study cohorts with no device- or procedure-related adverse events. Independent photo review showed greatest mean GAIS score for the Cryolipolysis + EMMS cohort followed by Cryolipolysis only, then EMMS only cohort. BSQ showed greatest average score increase for Cryolipolysis + EMMS cohort followed by Cryolipolysis only cohort, then EMMS only cohort. Mean circumferential reduction measurements were greatest for Cryolipolysis + EMMS cohort followed by Cryolipolysis only, and then EMMS only cohort. The mean SGAIS improvement score was equal for the Cryolipolysis only and Cryolipolysis + EMMS cohorts, followed by the EMMS only cohort.
A multimodal approach using cryolipolysis and EMMS was safe and demonstrated enhanced body contouring efficacy for this feasibility study.

Hypoglycemia hinders optimal glycemic management in type 1 diabetes (T1D). Long diabetes duration and hypoglycemia impair hormonal counter-regulatory responses to hypoglycemia. Our study was designed to test whether (1) the metabolic responses and insulin sensitivity are impaired, and (2) whether they are affected by short-lived antecedent hypoglycemia in participants with T1D.
In a randomized, crossover, 2x2 factorial design, 9 male participants with T1D and 9 comparable control participants underwent 30 minutes of hypoglycemia (p-glucose < 2.9 mmol/L) followed by a euglycemic clamp on 2 separate interventions: with and without 30 minutes of hypoglycemia the day before the study day.
During both interventions insulin sensitivity was consistently lower, while counter-regulatory hormones were reduced, with 75% lower glucagon and 50% lower epinephrine during hypoglycemia in participants with T1D, who also displayed 40% lower lactate and 5- to 10-fold increased ketone body concentrations following hypoglycemia, whereas palmitate and glucose turnover, forearm glucose uptake, and substrate oxidation did not differ between the groups. In participants with T1D, adipose tissue phosphatase and tensin homolog (PTEN) content, hormone-sensitive lipase (HSL) phosphorylation, and muscle glucose transporter type 4 (GLUT4) content were decreased compared with controls. And antecedent hypoglycemic episodes lasting 30 minutes did not affect counter-regulation or insulin sensitivity.
Participants with T1D displayed insulin resistance and impaired hormonal counter-regulation during hypoglycemia, whereas glucose and fatty acid fluxes were intact and ketogenic responses were amplified. We observed subtle alterations of intracellular signaling and no effect of short-lived antecedent hypoglycemia on subsequent counter-regulation. This plausibly reflects the presence of insulin resistance and implies that T1D is a condition with defective hormonal but preserved metabolic responsiveness to short-lived hypoglycemia.

OBJECTIVE: Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancer patients.
METHODS: Pre-surgery plasma samples from 212 patients (stage I-IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival.
RESULTS: In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA: pFDR range 0.017-0.049; TFA: pFDR range 0.029-0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (phet range: 0.00044-0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio [HR], 9.05; 95% confidence interval [CI] 2.17-37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04-0.87; phet = 0.00044).
CONCLUSIONS: These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.