Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • Adipose tissue can be divided into at least

    2020-07-31

    Adipose tissue can be divided into at least two metabolically-distinct types: brown adipose tissue (BAT) and white adipose tissue (WAT). BAT is primarily an energy expending tissue, whose human relevance has recently become an active area of research [3], [4]. White adipose tissue, in contrast, is primarily an energy storing tissue. White adipose tissue has been shown to have regional variation based on anatomical location in humans [5], [6]. Some of the most striking differences in WAT are observed between (abdominal) subcutaneous and visceral white adipose tissue. Accumulation of visceral adipose tissue, i.e. central obesity, has been associated with insulin resistance, metabolic syndrome, and Conessine mg [6], [7], [8]. By contrast, accumulation of subcutaneous adipose tissue has been associated with metabolically beneficial characteristics, including increased insulin sensitivity and decreased inflammation [7], [9]. White adipose tissue from other regions, such as gluteal adipose tissue, perirenal fat, and bone marrow, also have different properties, including differences in cytokine response and proliferation rates [10], [11]. This regional variation within white adipose tissue stresses the need to understand the underlying mechanisms accounting for differences in white adipose depots in order to develop targeted therapies for diabetes, lipodystrophy, and related metabolic complications. Several molecular differences between visceral and subcutaneous adipose tissue have been described. One of the most demarcating differences between adipose depots is the signature of developmental genes, including Hox, Shox, and T-box genes [12], [13]. Lineage tracing studies have revealed key developmental signatures in adipocyte development, such as the Myf5 lineage marking brown adipocytes and a subset of white adipocytes across different fat depots [14], [15]. The mesodermal developmental gene TBX15 has also been shown to mark a subset of white adipocytes which have a higher glycolytic rate [16]. Traditionally, surface markers have been used to establish region specificity and to distinguish adipocyte-lineage cells from other adipose-resident cells, although there is disagreement over the exact panel of surface marker expression in the adipocyte lineage [17], [18]. More extensive reviews on this topic are provided elsewhere [2], [19], [20]. Membrane metallo-endopeptidase (MME/Neprilysin/CD10/CALLA) is a membrane-bound protein with a distinct extracellular protease domain. MME was first isolated from rabbit kidney and described as a thermolysin-like enzyme [21]. Since then, MME has been shown to be well-conserved across different species from C.¬†elegans to mammals [22]. MME is a zinc metalloprotease and shares substrates and structural similarity with several related extracellular proteases, including Endothelin Converting Enzyme 1 (ECE1), Phosphate-regulating neutral endopeptidase X-linked (PHEX), and Kell blood group antigen (KEL) [23], [24], [25]. MME is also expressed in the brain, where the MME knockout mouse has been shown to have an increase in amyloidő≤ peptides, suggesting that MME may play a role in protection from Alzheimer\'s disease [26]. The whole-body MME knockout (MMEKO) mouse was created in 1995 and was described as a septic shock model because it showed hypersensitivity to treatment with different cytokines [27].