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SUMMARY:Brown adipose tissue – new option in the therapy of metabolic di
 sease?
DTSTART:20180315T093000
DTEND:20180315T103000
DTSTAMP:20260916T034721Z
UID:f680b3f7bcc606f01734471d2bf5ce16828af66e302e914a31997dd8
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Jörg HEEREN\, University Medical Center Hamburg Eppendo
 rf\, Germany\nSEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION
  ALLIANCE (LIMNA)\n\nAbstract:\nThe recent “re-discovery” of brown adi
 pose tissue (BAT) in humans is one of the most intriguing findings in the 
 research area of metabolic diseases as it raised hope for the treatment of
  obesity. In addition to brown adipocytes present in BAT depots\, inducibl
 e brown-like adipocytes so called beige adipocytes can be found in specifi
 c WAT depots under various catabolic conditions such as cold exposure in w
 intertime. Cold-activated beige and brown adipocytes trigger an energy-dem
 anding process known as adaptive thermogenesis\, which requires increased 
 uptake of dietary carbohydrates and lipids for maintaining caloric balance
 . The relevance of BAT is exemplified by the fact that in rodents\, BAT an
 d liver take up equal amount of energy from the bloodstream\, a process wh
 ich is able to normalize glucose and lipid values in insulin resistant and
  hyperlipidemic mice. Notably\, also in humans most of the standard metabo
 lic parameters routinely determined by physicians such as glucose and bloo
 d lipids are influenced by brown and beige adipocyte activity.\n\nRecently
 \, we investigated in more detail the regulation as well as the molecular 
 processes of lipid disposal into activated BAT\, using pharmacological and
  genetic interventions in mice. We found that short-term BAT activation by
  cold exposure or beta-3-adrenergic receptor agonism triggers insulin secr
 etion\, a process depending on fatty acid release by white adipose tissue.
  Furthermore\, we showed that both insulin release and brown adipocytes in
 sulin sensitivity is essential for the replenishment of endogenous energy 
 stores and efficient adaptive thermogenesis. These data demonstrate that b
 oth catabolic and anabolic processes are important for energy balance and 
 function of BAT. In addition to increased fatty acid disposal\, we found e
 nhanced uptake of dietary cholesterol into activated BAT as consequence of
  lipoprotein internalization. Following the fate of cholesterol\, we obser
 ved the induction of hepatic bile acid synthesis\, interestingly via the a
 lternative but not the classical pathway. This process\, depending on hepa
 tic CYP7B1 induction\, results in elevated plasma levels and pronounced fe
 cal excretion of conjugated bile acids\, accompanied by distinct changes i
 n gut microbiota. Pharmacological intervention using ezetimibe\, a drug bl
 ocking dietary cholesterol uptake\, prevented both the rise in bile acid e
 xcretion and compositional changes in gut bacteria in response to cold. Th
 ese results identify bile acids generated in the liver as the determinant 
 of cold-induced gut microbiota\, highlighting the relevance of cholesterol
  metabolism by the host for diet-induced changes on gut microbiota and ene
 rgy metabolism.\n\nAltogether\, our results demonstrate the functional rel
 evance of thermogenic adipocytes for systemic energy and lipoprotein metab
 olism. In this light\, increasing adaptive thermogenesis may represent a p
 romising therapeutic approach for obesity-associated metabolic diseases.\n
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LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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