Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.

• Klíčová slova
• Adipocyte differentiation, Endocrine disruptor, Obesity, Obesogen, Weight gain,
• MeSH
• adipogeneze MeSH
• endokrinní disruptory * toxicita   MeSH
• lidé MeSH
• obezita etiologie   MeSH
• předškolní dítě MeSH
• tuková tkáň MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• endokrinní disruptory * MeSH

Nonalcoholic fatty liver disease (NAFLD) is a growing concern worldwide, affecting 25% of the global population. NAFLD is a multifactorial disease with a broad spectrum of pathology includes steatosis, which gradually progresses to a more severe condition such as nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and eventually leads to hepatic cancer. Several risk factors, including exposure to environmental toxicants, are involved in the development and progression of NAFLD. Environmental factors may promote the development and progression of NAFLD by various biological alterations, including mitochondrial dysfunction, reactive oxygen species production, nuclear receptors dysregulation, and interference in inflammatory and immune-mediated signaling. Moreover, environmental contaminants can influence immune responses by impairing the immune system's components and, ultimately, disease susceptibility. Flame retardants (FRs) are anthropogenic chemicals or mixtures that are being used to inhibit or delay the spread of fire. FRs have been employed in several household and outdoor products; therefore, human exposure is unavoidable. In this review, we summarized the potential mechanisms of FRs-associated immune and inflammatory signaling and their possible contribution to the development and progression of NAFLD, with an emphasis on FRs-mediated interferon signaling. Knowledge gaps are identified, and emerging pharmacotherapeutic molecules targeting the immune and inflammatory signaling for NAFLD are also discussed.

• Klíčová slova
• cytokines, flame retardants, interferon, metabolic disruption, metabolism-disrupting chemicals, nonalcoholic fatty liver disease,
• MeSH
• biologické markery MeSH
• cílená molekulární terapie MeSH
• cytokiny metabolismus   MeSH
• interferony metabolismus   MeSH
• játra účinky léků   metabolismus   patologie   MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• náchylnost k nemoci * MeSH
• nealkoholová steatóza jater etiologie   metabolismus   patologie   MeSH
• objevování léků MeSH
• retardanty hoření škodlivé účinky   MeSH
• signální transdukce * MeSH
• zánět etiologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• interferony MeSH
• mediátory zánětu MeSH
• retardanty hoření MeSH