The Underappreciated Role of Intestinal Fat Storage

Could a “fatty intestine” be related to insulin resistance and energy balance? These and other provocative questions were addressed by Dr. Elizabeth Parks last Saturday evening at Experimental Biology in San Diego. Organized by the Energy and Macronutrients Research Interest Section, Dr. Parks gave a seminar titled, “Going with your gut: Individual responses in dietary fat absorption.”

Dr. Parks’ research often focuses on the cephalic phase of digestion – or the early physiological response before food is even ingested. She presented a story that led her to her current path: Teff and Engelman demonstrated in 1996 with a sham feeding model that taste has an important effect on glucose metabolism and, in 2002, Robertson and colleagues published data showing that, compared to a high fat meal, consuming a high carbohydrate meal at night resulted in better glucose tolerance in the morning. Concurrently, they demonstrated a high fat meal at night yields a better fat tolerance the following day. These data suggest that there is some adaptive priming occurring and that, as Dr. Parks put it, “you best metabolize what you’ve just eaten.” She noted that we need to better match the challenge test with the eating pattern of interest.

In 2003, Robertson and colleagues published the results of an experiment in 10 healthy participants scheduled for an endoscopy who were fed a high fat meal, then 5 hours later were fed 50 grams of fat with either 38 grams of glucose or water. The participants who consumed the glucose along with the fat in the second meal showed less lipid in the jejunum. In other words, some dietary fat was stored in the intestine from a meal and its release was accelerated when glucose in combination with fat was consumed. Since then, Dr. Parks and others have shown that simply tasting fat without ingesting it, or just consuming carbohydrate, can cause an early rise in chylomicron secretion and blood triglyceride levels. This means that the intestine stores some of the fat from previous meals; in fact, Parks estimates that  ⅕ to ¼ of the fat in your meal is stored in the intestine for at least 16 hours, and it is released in response to taste. Their data also suggests that body fat is negatively correlated with the amount of fat coming from the intestine and entering the blood at a subsequent meal. If intestinal fat stores serve a regulatory function to control energy balance (by releasing in response to taste), this raises the possibility that the mechanism that controls how much is release is perturbed.

Parks then discussed research supporting that we can taste fat. As further evidence, they have scoured literature for kinetic data and devised a mathematical model to show that rate of release of fat from the gut is consistent with the idea that this physiological response is due to our ability to taste fat. She also noted that chylomicrons may be supported in the absence of dietary fat by fatty acids in circulation entering the enterocyte, being packaged into chylomicrons, and secreted. Some data suggest that high free fatty acids increase the contribution from plasma to chylomicrons.

Dr. Parks has also been asking: does the rate of fat absorption impact health? Dr. Jennifer Lambert and Parks have unpublished data showing that the time-course of triglyceride absorption between people can vary substantially – about 1 to 4 hours. She showed graphs of the fat absorption curves of individual participants, and the patterns were often variable, emphasizing that much remains to be understood about why this occurs. Finally, she showed that stratifying by an early or late absorption peak revealed differences in participants in each group. For example, participants with an early peak tended to be more insulin resistant than those with a later peak.

Dr. Parks has been innovative in her use of stable isotopes for exploring lipid metabolism in health and disease. Clearly the intestine is an underappreciated tissue in fat storage and we are just on the cusp of understanding the role in which it mediates health and energy balance.