@article{PueschelKlauderHenkelOberlaender2022,
  author    = {P{\"u}schel, Gerhard and Klauder, Julia and Henkel-Oberl{\"a}nder, Janin},
  title     = {Macrophages, low-grade inflammation, insulin resistance and hyperinsulinemia},
  series = {Journal of Clinical Medicine : open access journal},
  volume    = {11},
  journal   = {Journal of Clinical Medicine : open access journal},
  number    = {15},
  publisher = {MDPI},
  address   = {Basel, Schweiz},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11154358},
  pages     = {1 -- 30},
  year      = {2022},
  abstract  = {Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the resident macrophage pool as well as newly recruited monocyte-derived macrophages are important drivers in the development of low-grade inflammation. While metabolic dysfunction, insulin resistance and tissue damage may trigger or advance pro-inflammatory responses in macrophages, the inflammation itself contributes to the development of insulin resistance and the resulting hyperinsulinemia. Macrophages express insulin receptors whose downstream signaling networks share a number of knots with the signaling pathways of pattern recognition and cytokine receptors, which shape macrophage polarity. The shared knots allow insulin to enhance or attenuate both pro-inflammatory and anti-inflammatory macrophage responses. This supposedly physiological function may be impaired by hyperinsulinemia or insulin resistance in macrophages. This review discusses the mutual ambiguous relationship of low-grade inflammation, insulin resistance, hyperinsulinemia and the insulin-dependent modulation of macrophage activity with a focus on adipose tissue and liver.},
  language  = {en}
}
@article{HenkelOberlaenderKlauderStatzetal.2021,
  author    = {Henkel-Oberl{\"a}nder, Janin and Klauder, Julia and Statz, Meike and Wohlenberg, Anne-Sophie and Kuipers, Sonja and Vahrenbrink, Madita and P{\"u}schel, Gerhard},
  title     = {Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin E₂},
  series = {Biomedicines : open access journal},
  volume    = {9},
  journal   = {Biomedicines : open access journal},
  number    = {5},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines9050449},
  pages     = {10},
  year      = {2021},
  abstract  = {Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E₂ (PGE₂) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE₂ to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE₂ synthesis. PGE₂ in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE₂ in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.},
  language  = {en}
}
@article{BishopMachateHenningetal.2022,
  author    = {Bishop, Christopher Allen and Machate, Tina and Henning, Thorsten and Henkel-Oberl{\"a}nder, Janin and P{\"u}schel, Gerhard and Weber, Daniela and Grune, Tilman and Klaus, Susanne and Weitkunat, Karolin},
  title     = {Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle},
  series = {Nutrition \& Diabetes},
  volume    = {12},
  journal   = {Nutrition \& Diabetes},
  number    = {1},
  publisher = {Nature Publishing Group},
  address   = {London},
  issn      = {2044-4052},
  doi       = {10.1038/s41387-022-00200-8},
  pages     = {9},
  year      = {2022},
  abstract  = {Objective: Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. Methods: To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes). Results: Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure-likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/ insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling. Conclusion: These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.},
  language  = {en}
}