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Cited by 124Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Adipose tissue and metabolic alterations: regional differences in fat cell size and number matter, but differently: a cross-sectional study.

Rydén, Mikael, Andersson, Daniel P., Bergström, Ingrid B., Arner, Peter·2014·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2014-1526
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Abstract

OBJECTIVE: White adipose tissue can expand by increasing the size and/or number of fat cells. Although increased sc and visceral fat cell size associates with an adverse metabolic profile, the relationship with fat cell number in either depot is unknown. We hypothesized that adipocyte number and size displayed different relationships with clinically relevant metabolic variables. METHODS: This was a cross-sectional study of 204 patients scheduled for gastric bypass surgery. Fat cell size and number were determined in visceral and abdominal sc adipose tissue and related to insulin sensitivity (by hyperinsulinemic euglycemic clamp), fasting plasma levels of insulin, triglycerides and high-density lipoprotein (HDL) cholesterol. RESULTS: Visceral and sc fat cell volumes were positively correlated with insulin and triglyceride levels and negatively with insulin sensitivity and HDL-cholesterol (P = .0020 or better). In contrast, although visceral fat cell number did not associate with any metabolic parameter, sc adipocyte number displayed a positive association with insulin sensitivity and HDL-cholesterol and a negative relationship with insulin and triglyceride levels (P = .0014 or better). All results were independent of body fat mass. CONCLUSIONS: Variations in fat cell size and number correlate differently with metabolic parameters in obesity. Increased fat cell size in visceral and sc depots associates with a pernicious metabolic profile, whereas increased sc, but not visceral, fat cell number correlates with a more beneficial phenotype. Whether determination of sc fat cell number, in addition to adipocyte size, may have a predictive value for the risk of type 2 diabetes needs to be demonstrated in prospective or mechanistic studies.

AI snapshot

Written from the paper’s full text.

TL;DR

In 204 patients undergoing gastric bypass, visceral and subcutaneous fat cell volume associated with a worse metabolic profile, while subcutaneous fat cell number associated with a more favorable insulin/lipid profile. These relationships were independent of total body fat mass, but the cross-sectional design cannot establish causality.

Key findings

  • Visceral and subcutaneous fat cell volume correlated positively with plasma insulin and triglycerides and negatively with insulin sensitivity and HDL-cholesterol (P = .0020 or better). For example, visceral fat cell volume vs plasma insulin: r = 0.45, P < .0001; vs insulin sensitivity: r = −0.42, P < .0001.
  • Visceral fat cell number did not associate with any studied metabolic parameter (e.g., plasma insulin r = −0.080, P = .28; insulin sensitivity r = −0.0038, P = .96).
  • Subcutaneous fat cell number showed the opposite pattern from fat cell volume: positive with insulin sensitivity (r = 0.25, P = .0014) and HDL-cholesterol (r = 0.29, P < .0001), negative with plasma insulin (r = −0.26, P = .0003) and triglycerides (r = −0.35, P < .0001).
  • In multiple linear regression corrected for total body fat, subcutaneous fat cell number remained associated with plasma insulin (Std β = −0.34, P < .0001), insulin sensitivity (Std β = 0.31, P = .0002), triglycerides (Std β = −0.38, P < .0001), and HDL-cholesterol (Std β = 0.35, P < .0001).

Methods

  • Cross-sectional study of 204 patients referred for Roux-en-Y gastric bypass surgery (age 18–60 years; BMI >30 kg/m² with obesity-related complications or BMI >35 kg/m²); ESAT/EVAT values were obtainable from 188 subjects.
  • Abdominal subcutaneous fat biopsy was obtained by needle aspiration, and visceral fat biopsy from the greater omentum during surgery. Fat cell size was determined by measuring 100 isolated adipocytes; fat cell number was estimated from depot weight divided by mean fat cell weight.
  • Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp; fasting plasma insulin, triglycerides, and HDL-cholesterol were measured. DEXA with CoreScan estimated visceral and subcutaneous abdominal fat masses. Analyses used Spearman correlation, ANCOVA, and multiple linear regression, with Bonferroni correction.

Limitations

  • The paper states that correlations ranged from −0.5 to +0.5, suggesting relatively large interindividual differences in adipocyte size/number are needed to observe metabolic differences; the cohort was rather homogeneous, predominantly women, and larger studies including normal-weight subjects and more men might yield different or stronger correlations.
  • The paper states that fat cell number is calculated from two independent parameters (depot size and mean adipocyte weight), so determinations are only relevant for ESAT and EVAT; DEXA/CoreScan measures are indirect, and no visceral adipose tissue phantom was used for calibration.
  • The paper states that only a limited set of metabolic phenotypes was studied, the cohort included T2DM and/or hypertension with gender imbalance, and predictive/causal relationships require prospective or mechanistic validation. Evident from the text: the cross-sectional design cannot establish causality, and the bariatric-surgery population may not represent obese individuals in the general population.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/jc.2014-1526

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 37 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    When corrected for gender, diabetes, or hypertension, the observed correlations remained statistically significant with nominal P values < .05.

    “Nevertheless, when corrected for gender, diabetes, or hypertension, the observed correlations remained statistically significant with nominal P values Ͻ .05.”
    Quote in the paperSubstantial claim
  • Findingown data

    The same correlations remained significant if the Bonferroni correction was used (allowing P < .0042 to be significant).

    “The same was true if the Bonferroni correction was used (allowing P Ͻ .0042 to be significant).”
    Quote in the paperSubstantial claim
  • Findingown data

    In subcutaneous adipose tissue of obese subjects, fat cell volume showed correlations with insulin sensitivity and plasma levels of insulin, triglycerides, and HDL-cholesterol that were similar to those of visceral fat cell volume.

    “In sc adipose tissue, similar correlations were observed regarding fat cell volume as for visceral adipose tissue (Table 2 and Figure 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    After Bonferroni correction of P values in Table 2 (16 comparisons allowing P < .0031 to be significant), all significant correlations remained.

    “After Bonferroni correction of P values in Table 2 (16 comparisons allowing P Ͻ .0031 to be significant), all significant correlations remained.”
    Quote in the paperSubstantial claim
  • Findingown data

    All correlations between subcutaneous fat cell volume/number, visceral adipocyte volume, and metabolic variables remained statistically significant after correction for total body fat in kilograms.

    “All correlations remained statistically significant after correction for total body fat expressed in kilograms (or as percentage of total body weight, values not shown).”
    Quote in the paperSubstantial claim
  • May combine two claims. 17
  • Classified as probably not a substantial claim. 21

  • May combine two claims.

    Findingown data

    In subcutaneous adipose tissue of obese subjects, fat cell number was positively related to insulin sensitivity and HDL-cholesterol and negatively related to insulin and triglycerides.

    “Thus, there was a positive relationship with insulin sensitivity and HDL-cholesterol and a negative relationship with insulin and triglycerides.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In subcutaneous adipose tissue of obese subjects, fat cell number was significantly correlated with all studied metabolic variables, but in the opposite direction to fat cell volume.

    “In contrast, although sc fat cell number correlated significantly with all variables, it did so in an opposite way compared with cell volume (Table 2 and Figure 2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Numerically similar correlations and P values were obtained if insulin sensitivity was corrected for lean body mass.

    “Furthermore, numerically similar and P values were obtained if insulin sensitivity was corrected for LBM (M/LBM, values not shown).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    The present study suggests that classifying overweight/obese patients according to their fat cell size and number might be clinically useful to estimate the risk of T2DM and related metabolic complications and thereby determine treatment strategies, at least in specialized clinics.

    “The present study suggest that classifying overweight/obese patients according to their fat cell size and number might be clinically useful to estimate the risk of T2DM and related metabolic complications and thereby determine treatment strategies, at least in specialized clinics.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Increased subcutaneous or visceral fat cell size correlates with an adverse insulin/lipid profile, whereas increased subcutaneous fat cell number is coupled to a less pernicious phenotype.

    “Increased sc or visceral fat cell size correlates with an adverse insulin/lipid profile, whereas increased sc fat cell number is coupled to a less pernicious phenotype.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In abdominal subcutaneous fat, more adipocytes is related to a more favorable state, whereas fat cell number in the visceral depot does not correlate with any of the studied metabolic parameters.

    “In abdominal sc fat, more adipocytes is related to a more favorable state, whereas fat cell number in the visceral depot does not correlate with any of the studied metabolic parameters.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Adipose inflammation has emerged as an important factor contributing to insulin resistance.

    “Adipose inflammation has emerged as an important factor contributing to insulin resistance (27).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It is relatively easy to measure fat cell size in small subcutaneous needle biopsies.

    “It is relatively easy to measure fat cell size in small sc needle biopsies (40), and fat mass in different regions can be assessed by DEXA, with the use of recently developed software.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Fat mass in different regions can be assessed by DEXA with recently developed software.

    “It is relatively easy to measure fat cell size in small sc needle biopsies (40), and fat mass in different regions can be assessed by DEXA, with the use of recently developed software.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    One subject was examined using different DEXA equipment, and in one individual, DEXA measurements were missing.

    “One subject was examined using different DEXA equipment, and in one individual, DEXA measurements were missing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A limitation of the study is that no visceral adipose tissue phantom was used for calibrations.

    “Nevertheless, a limitation of our study is that no visceral adipose tissue phantom was used for calibrations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The cohort included participants with non-insulin-dependent diabetes and/or hypertension, and there was a clear imbalance in gender.

    “Moreover, our cohort included participants with non-insulin-dependent diabetes (T2DM) and/or hypertension, and there was a clear imbalance in gender.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Adipocyte size correlates closely with the expression and secretion of the proinflammatory cytokine TNFα in lean healthy women and with insulin resistance/hyperlipidemia in morbidly obese women.

    “Interestingly, adipocyte size correlates closely with the expression and secretion of the proinflammatory cytokine TNF␣ in lean healthy women (28) and insulin resistance/hyperlipidemia in morbidly obese women (14).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28]

      Not checked in the free run.

    • cites [14]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The capacity of adipose tissue to store lipids is limited.

    “A related possibility explaining the association between adipose cellularity and metabolic changes may be that the capacity of adipose tissue to store lipids is limited (32).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The subjects were scanned using standard imaging and positioning protocols and the same scan mode (set for obese subjects) was used throughout the study.

    “The subjects were scanned using standard imaging and positioning protocols and the same scan mode (set for obese subjects) was used throughout the study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Up to one-third of overweight or obese subjects are metabolically healthy.

    “Up to one-third of overweight or obese subjects are metabolically healthy (37).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    In multiple regression analyses, normal distribution of residual error was determined using Shapiro-Wilk W test and constant variance checked.

    “In the multiple regression analyses, normal distribution of the residual error was determined using the Shapiro-Wilk W test and the constant variance of the errors was further checked by rando/mLy distributed patterns in residual-by-predicted plots.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The study validated the DEXA CoreScan method in an independent cohort of obese women and men, comparing the weight of the greater omentum with visceral adipose tissue mass estimated using DEXA and CT.

    “We subsequently validated this in an independent cohort of obese women and men, comparing the weight of the greater omentum with visceral adipose tissue mass estimated using the presently used DEXA equipment/software and CT (22).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    It has been suggested that the classical categorization of body fat status based on BMI and adipose distribution is insufficient.

    “It has been suggested that the classical categorization of body fat status based on BMI and adipose distribution is insufficient (36).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Surgical removal of large amounts of abdominal subcutaneous adipose tissue from obese patients does not improve insulin resistance or other metabolic abnormalities.

    “Furthermore, surgical removal of large amounts of abdominal sc adipose tissue from obese patients does not improve insulin resistance or other metabolic abnormalities (7, 8).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7]

      Not checked in the free run.

    • cites [8]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The Bonferroni test was used to correct for multiple comparison statistics in Tables 2 and 3.

    “The Bonferroni test was used to correct for multiple comparison statistics in Tables 2 and 3.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    No hardware or software changes were made during the course of the trial.

    “No hardware or software changes were made during the course of the trial.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Automatic calibration checks of the DEXA were performed daily, and thrice-weekly calibrations using a spine phantom were performed.

    “Automatic calibration checks of the DEXA were performed daily throughout the study, and thrice-weekly calibrations using a spine phantom (for bone mineral density, provided by the manufacturer) were performed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    In total, 204 subjects were included in the study where ESAT/EVAT values from 188 subjects could be obtained.

    “In total, 204 subjects were included in the study where ESAT/EVAT values from 188 subjects could be obtained.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In 14 patients, EVAT and ESAT values could not be measured because of severe obesity.

    “In 14 patients, EVAT and ESAT values could not be measured because of the severe obesity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Subjects with many small subcutaneous fat cells displayed lower TNFα secretion and better insulin sensitivity.

    “In these studies, subjects with many small sc fat cells displayed lower TNF␣ secretion and better insulin sensitivity, respectively.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28]

      Not checked in the free run.

    • cites [14]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When adipose expansion reaches a maximum, lipids are stored ectopically in skeletal muscle, liver, and pancreatic islets, which leads to lipotoxic effects including abnormal lipoprotein metabolism, insulin dysfunction, and altered insulin secretion.

    “Consequently, when adipose expansion reaches a maximum, lipids are stored ectopically in skeletal muscle, liver, and pancreatic islets, which in turn leads to lipotoxic effects including abnormal lipoprotein metabolism, insulin dysfunction, and altered insulin secretion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Fat cell volume and weight were determined using a standard method in the field.

    “Fat cell volume and weight were determined using a standard method in the field that has been described in detail previously (14,22).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14]

      Not checked in the free run.

    • cites [22]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The association between body fat distribution and insulin resistance/T2DM is controversial.

    “Furthermore, the association between body fat distribution and insulin resistance/T2DM is controversial (38,39).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [38]

      Not checked in the free run.

    • cites [39]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Because only total android fat mass and EVAT are used to determine ESAT and both are valid measures, the calculation of ESAT should be valid.

    “Because only total android fat mass and EVAT are used to determine ESAT and both are valid measures, it follows that also the calculation of ESAT should be valid.”
    Quote in the paperSubstantial claim
30 of 30

  • The paper relies on this without support.

    The relationship between adipocyte number and insulin resistance and other metabolic variables associated with T2DM risk was unknown at the time of the study.

    “However, the relationship between adipocyte number and insulin resistance as well as other metabolic variables associated with T2DM risk is unknown.”

  • The authors state this as an assumption.

    Mean fat cell weight can be obtained by multiplying fat cell volume by 0.915, assuming fat cell density equals that of human adipose triglycerides.

    “Assuming a mean density of fat cells equal to that of human adipose triglycerides, mean fat cell weight was obtained by multiplying the volume by 0.915 (ie, the density in grams per milliliter of triolein).”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • AT content and function differ markedly between obese and healthy lean people, regardless of localization.

    “Regardless of its localization, AT content and function differ markedly between obese and healthy lean people”

    From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Rydén et al., 2014

    The Abstract describes measurements of subcutaneous and visceral fat in obese subjects, but not a comparison with healthy lean people. The Discussion says that including normal-weight subjects might yield different results. I searched for lean and normal-weight comparators; the copy does not establish the claimed difference in adipose-tissue content and function regardless of location. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Cites

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1 of the 43 references couldn’t be matched to a known paper.

Cited by

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Related

Authors
Rydén, M., Andersson, D. P., Bergström, I. B., & Arner, P.
Affiliations
Karolinska University Hospital (SE)
Corresponding author
Rydén, Mikael
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2014-10
Volume
99
Issue
10
Pages
E1870-E1876
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2014-1526
OpenAlex
W2114647414
Semantic Scholar
d4539851f822e7fab616919f43ad2e7b017805f4
Cited by
124
References
43
Citations by year
2026: 7 · 2025: 8 · 2024: 10 · 2023: 10 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 18 · 2017: 12 · 2016: 4 · 2015: 15
FWCI
7.81
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Eli Lilly and Company
  • Karolinska Institutet
  • Novo Nordisk
  • Vetenskapsrådet
  • European Association for the Study of Diabetes
  • Novo Nordisk Fonden (NNF14OC0010187, NNF12OC1016371)
  • U.S. Food and Drug Administration
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
white adipose tissue, adipocyte size, adipocyte number, visceral adipose tissue, subcutaneous adipose tissue, insulin sensitivity, insulin resistance, type 2 diabetes risk, HDL cholesterol, triglycerides, obesity, gastric bypass, metabolic phenotypes
MeSH terms
Adolescent, Adult, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Insulin, Insulin Resistance, Cholesterol, HDL, Male, Middle Aged, Obesity, Morbid, Omentum, Triglycerides, Glucose Clamp Technique, Adipocytes, Cell Size, Subcutaneous Fat, Intra-Abdominal Fat, Young Adult, Preoperative Period

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