Episode 36 – Metabolic Syndrome Chapter 2: leptin

Show notes:

  • [2m30s] Raphael explains that leptin and insulin have a lot of mechanistic overlap in terms of managing fat storage and energy distribution, making them crucial players in metabolic syndrome.
  • [3m20s] Gabor explains that he lost interest in leptin a few back after concluding that it all seemed to happen downstream of insulin (further away from foundational cause(s)).
  • [4m30s] Gabor talks about a study describing how leptin regulates the glucose-fatty acid cycle (see Lower Insulin Facebook group discussion of this)
  • [5min] Gabor talks about another study on leptin, this time how triglycerides cross the blood–brain barrier and induce central leptin and insulin receptor resistance (see Lower Insulin Facebook group discussion of this)
  • [5m50s] Raphael gives some background on leptin
    • Leptin from the Latin leptos meaning “thin”
    • In 1949 Jackson lab mice were bred with a double-mutation in the ob gene, making them unable to produce the leptin protein, hence ob/ob mice are known to be fat and hyperphagic (they eat a ton)
    • Leptin circulates in blood both free from and bound to proteins
  • [9m55s] Raphael notes that insulin can cause its own resistance, as can leptin. He’s confused as to why some people think insulin is exempt from this.
  • [12m5s] Raphael reads a paragraph from a post by Peter of Hyperlipid nicely summarizing what’s meant by leptin being ‘higher level signalling’; it’s less fundamental, more downstream in the causal chain than say, the mitochondrial electron transport chain.
  • [16m20s] Raphael asks Gabor how adipocyte size and leptin release and/or concentration correlate, or not, with one another?
  • [24m23s] Raphael talks about how much of leptin’s action is insulin independent and asks Gabor about it.
  • [29m55s] Raphael talks about diabetic ketoacidosis (not to be confused with ketosis!) and the relevant paper
  • [30m45s] Raphael mentions how this Perry & Shulman et al. paper is not recognizing the findings by the Kieffer lab (see this paper) regarding which of leptin’s effects are insulin independent or not.
  • [37m30s] Raphael points out that the increase in leptin after feeding correlates with a decrease in hepatic ketogenesis, which makes sense given leptin is a ‘fed’ signal.
  • [40min] Gabor explains why he thinks “it’s all adipocyte size” when it comes to determining our risk for metabolic syndrome.
  • [43m50s] Raphael talks about how lipodystrophy informs us about the importance of adipose tissue function; managing energy surges and dips the body encounters.
  • [46m45s] Gabor talks about how he thinks of the hierarchy of causes of metabolic diseases; leptin vs insulin vs mitochondria vs …. And how looking beyond cellular factors, such as environmental causes, is crucial to filling in the causal chain of disease etiology.

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