Episode 27 – Adipocytes and insulin resistance

Show notes:

  • 60% of US adults are overweight to moderately obese but within that group there is great heterogeneity in their response to insulin ⇒ their degree of insulin sensitivity can vary more than sixfold at any given BMI within this range
  • Adults constantly form and replace adipose cells, called turnover
  • 2 places to measure fat are the femoral (leg fat) and subcutaneous (under your skin and predominantly white) adipose tissues
  • For IMGU (insulin mediated glucose uptake), the higher the SSPG (steady-state plasma glucose) concentration, the more IR the individual
  • Insulin sensitive people have
    • larger adipose cells
    • more (functional) small adipose cells
    • decreased expression of adipocyte-differentiation genes
  • A clue from animal lipodystrophy models about how insulin resistance manifests is that the absence of subcutaneous fat is associated with ectopic fat and severe insulin resistance

 

  • Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans (McLaughlin et al. 2016)
    • The study select for “overweight-to-moderately obese individuals classified as IS or IR” [insulin sensitive = IS; insulin resistant = IR]
    • SSPG assays were use to exclude moderately IS/IR people, leaving only the IS or IR
    • This was an overfeeding study by a whopping 880 kcals per day. This was so that “adipose cells would be near or at maximal storage capacity and […] would likely exhibit differential adipose cell and tissue responses to additional TG storage demands” [triglycerides = TG]
      • The overfeeding diet was 43% carbohydrate, 42% fat, and 15% protein
    • Prediction about the IS subjects ⇒ “due to enhanced ability to differentiate and recruit new adipose cells, would be protected from adipocyte hypertrophy, ectopic fat deposition, lipolysis, and/or worsening of insulin resistance”
    • Prediction about the the IR subjects⇒ “impaired adipocyte differentiation and TG storage, including adipocyte hypertrophy, lipolysis/increased circulating free fatty acid (FFA), fat deposition in visceral and intrahepatic depots, and worsening insulin resistance”
    • Results about the IR subjects
      • Correct “significantly larger peak diameter of fat cells” (hypertrophy)
      • Correct “greater percentage of small cells than the IS subjects” (adipocyte-specific hyperplasia)
      • Correct “VAT and %VAT were significantly greater in the IR subgroup” (visceral fat increased)
      • Correct “IHL was nearly eightfold greater” (liver fat increased)
      • “IR increased significantly in both groups (45% in the IS and 8% in the IR group)” ⇒ there was significantly more IR proportionally speaking in the insulin SENSITIVE group !
      • “The peak diameter [of the adipocytes] increased in both groups, but this change was only statistically significant in the IS group”
      • In contrast to our hypothesis that IS subjects would demonstrate adaptive adipose tissue and metabolic responses to weight gain, we found the opposite: IS subjects exhibited maladaptive adipose tissue responses and developed clinically significant insulin resistance
      • Worsening metabolic response “were independent of weight gain per se, implying that differential cellular and regional fat distribution patterns of adipose tissue may contribute to the metabolic heterogeneity of obesity
      • The authors noted a “paradox: although the IS subjects had a healthier adipose and metabolic profile at baseline, with the exception of TG and VLDL cholesterol, they decompensated to a greater degree with weight gain” ⇒ this remains hard to explain.
  • Association of in vivo adipose tissue cellular kinetics with markers of metabolic health in humans (White et al. 2017)
    • AT expandability hypothesis ⇒ a lack of hyperplasia [impaired proliferation] results in the limited capacity of AT to expand and store fat, causing metabolic derangements
    • This study found that no, it is in fact “hyperplastic expansion [high proliferation], that is associated with metabolic syndrome”

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