Trafficking of dietary fat and resistance to obesity

Abstract

The task of maintaining energy balance involves not only making sure that the number of calories ingested equals the number of calories burned but also involves ensuring nutrient balance. This means that over time, the quantity of carbohydrate, fat and protein consumed equals the amount of each oxidized. While the body has the ability to convert protein to carbohydrate and carbohydrate to fat, over long periods of time the body establishes nutrient balance with a high degree of accuracy storing excess nutrients as fat. To make decisions about food intake, the brain must assimilate information about the quantity of nutrients ingested and their disposition through the body over time. This is a very complex time ordered process as different tissues may be in different states of energy balance at different intervals following food ingestion. The fundamental task for the brain is to assess the influx of nutrients relative to stored pools of those nutrients and the rate at which they are being oxidized. It has been suggested that this task is particularly difficult for dietary fat because the stored pool of lipid is quite large compared to either the stored pools of carbohydrate and protein or the quantity of fat ingested per day. It is clear that some organisms resist weight gain even in the face of highly palatable diets. In fact most individuals eat less on any given day than they could given their maximal capacity for consumption. A central question then is: what restrains food intake in the setting of widely available highly palatable food? In this paper we will discuss the evidence that the movement of dietary fat between tissues may play an important role in the fidelity of nutrient sensing and as a result, resistance or susceptibility to obesity. In particular, the relative metabolism of dietary fat favoring oxidation over storage may be associated with more robust signaling of positive energy balance and resistance to dietary induced obesity in both humans and rats.

Figure 1

Oxidation of Dietary Fat in Lean, Obese and Reduced Obese Zucker Rats. The oxidation of an oleic acid tracer placed in a test meal over the 6 hours following the meal was determined from the appearance of ¹⁴CO₂ (previously published in ref. 4).

Figure 2

Tissue distribution of a dietary fat tracer in Adipose Tissue (AT), Skeletal Muscle (SM), Serum (Se), Liver (Li) and Gastrointestinal tract (GI) in previously fasted lean male Sprague Dawley rats. A test meal containing 14C oleate was administered at time 0 and the metabolic fate followed over 30 days. Each point represents data from 4–6 rats (previously published in ref. 5).

Figure 3

The tissue distribution of a dietary oleate tracer in the 10 days following the administration of a test meal in either the fasted (panel A) or previously fed (panel B) states (previously published in ref. 6).

Figure 4

The oxidation of dietary Linolenic, Oleic and Stearic acid tracers placed in a test meal administered to male Sprague Dawley rats that were previously either fasted (panel A) or Fed (panel B) (previously published in ref. 6).

Figure 5

The oxidation of a dietary fat tracer in male and female Obesity Prone (OP) and Obesity Resistant (OR) rats consuming a high carbohydrate Chow diet (panel A) and 5 days after the introduction of a high fat diet (HFD) (panel B) (previously published in ref. 29)

Figure 6

The effects of overfeeding on hunger as measured with visual analogue scores (VAS) in thin (OR) subjects and reduced obese (OP) subjects. Hunger was measured with VAS on a PDA before Breakfast (B), Lunch (L) and Dinner (D) during a 3 day baseline eucaloric period and for 3 days during which subjects were overfed 50% above basal energy needs (previously published in ref. 13)

Figure 7

Regional brain activation by fMRI in response to visual food stimuli of high hedonic value in thin (OR) subjects consuming a eucaloric diet. The results demonstrate significant activation of the inferior visual cortex, and hypothalamus.

Figure 8

Regional brain activation by fMRI in response to visual food stimuli of high hedonic value in thin (OR) subjects following 2 days of overfeeding at 30% above basal energy requirements. The results demonstrate a marked attenuation of the stimulation seen in a eucaloric state (these results were previously published in ref. 14).