PAI-1 deficiency and PAI-1 inhibitor treatment can protect against HFD-induced obesity, insulin resistance, and liver steatosis (113–115), partially via the enhanced energy expenditure associated with alleviated hypothalamic leptin resistance (116) and increased adipocyte lipolysis (114, 117). Here, SERPINE1 is linked to hyperinsulinemic hypoglycemia, familial, 4.