Top Highlights

• Prolonged hyperinsulinemia leads to an increase in leptin’s plasma concentration, while short-term hyperinsulinemia does not cause such a change
• Moreover, insulin infusion increases plasma leptin concentration in humans (50), and rodents with type 1 diabetes exhibit significantly reduced leptin levels
• t is assumed that insulin stimulates leptin production via glucose metabolism (51–53). The blockade of glucose transports or glycolysis in the presence of high insulin levels inhibits the expression and secretion of leptin in adipocyte
• Changes in glucose metabolism due to the application of a high-fat diet for 24 hours explain the reduced level of leptin in human circulation and thus contribute to a high-fat diet in promoting weight gain and obesity
• The reduced level of leptin in the circulation observed during high energy consumption is associated with humans’ hunger (45). Therefore, leptin flows from the adipocyte into the bloodstream, passes through the BBB, and arrives in areas of the brain involved in regulating the hypothalamus’s energy balance

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