Traditionally, the leading hypothesis regarding the development of
obesity involves caloric imbalance, whereby the amount of calories consumed exceeds the amount of calories burned which causes
obesity. Another hypothesis for why we get fat has surfaced in the last decade which is the idea that the overconsumption of added
sugars and refined
carbohydrates induce
insulin resistance and high
insulin levels causing
obesity. While
insulin is a fat-storing
hormone, this hypothesis does not explain visceral adiposity, or why certain people are found to have fat stored in and around their organs. We propose a new mechanism for body fattening, particular visceral adiposity. This hypothesis involves the overconsumption of
fructose, which leads to
inflammation in all cells that metabolize it rapidly. When
fructose is metabolized in subcutaneous adipocytes, the subsequent
inflammation leads to an increase in intracellular
cortisol in order to help squelch the
inflammation. Unfortunately, the increase in intracellular
cortisol leads to an increased flux of
fatty acids out of the subcutaneous adipocytes allowing more substrate for fat storage into visceral fat tissue. Moreover
fructose-induced
inflammation in the liver also leads to increased intracellular
cortisol via an upregulation of 11-B
hydroxysteroid dehydrogenase type 1 causing increased fat storage in the liver (i.e.,
fatty liver). In essence, the
fructose-induced inflammatory
cortisol response causes "thin on the outside, fat on the inside" (TOFI). Furthermore,
fructose in the brain, either from
fructose uptake via the blood brain barrier or endogenous formation from
glucose via the
polyol pathway stimulates an increased release of
cortisol causing hepatic gluconeogenesis leading to overall
insulin resistance and further body fattening. This review paper will discuss in detail the hypothesis that
fructose-induced
inflammation and
cortisol activation causes visceral adiposity.