3.3 CARACTERIZACIÓN BÁSICA DE LA LÍNEA DE TRANSMISIÓN
3.3.3 CARACTERÍSTICAS ELÉCTRICAS
3.3.3.3 Flujos de potencia
An imbalance in energy intake and energy expenditure is necessary to induce net body weight gain or a net body weight loss (Bray and York, 1979; Friedman and Halaas, 1998), However, variations in total energy intake of daily food is not the only factor in determining bodyweight; the macronutrient composition o f the diet also plays a major role in the development of such an energy imbalance (Flatt et al., 1988; Schütz et al., 1995), This may then be compensated by changes in body composition even if there is no net change in energy balance. In this context, it has been suggested that dietary fat promotes adipose accumulation more effectively than dietary carbohydrate (Danforth et al, 1985; Schütz et a l, 1989; Raben et al, 1996). Thus, high-fat diets can induce body weight and adiposity increases in humans (Astrup et al., 1994) and animals (Lim et al, 1991), High fat diets also contribute to insulin resistance (Reaven et al, 1967; Storlien et al., 1986), impaired glucose metabolism (Glueck et al., 1969), type 2 or non-insulin dependent diabetes mellitus (NIDDM) (Himsworth et al., 1935, Kolterman et al., 1979), stroke, and coronary artery disease (Lipid Research Clinics Program, 1984). Although the mechanisms underlying these issues are not clearly understood, many studies have tried to assess the effects o f such diets on individual biochemical and metabolic parameters or regulators in order to aid in this understanding. Experiments were therefore carried out in order to assess what effect a high fat diet would have in SLOB male and female rats.
( a ) T esticu lar fat pad
S GH
SLOB
S GH
NORM AL
(b)
S upra-renal fat pad(U * * 8
6
4 20
S GH S GH SLOB NORM AL (c) P lasm a leptin B 40^ I 30S
2 0-I
B c/3 cd a, 0. S GH SLOB1
S GH NORM ALF i^ r e 5.2 Effect of GH treatment on fat pad weight and plasma leptin levels in SLOB and normal male rats. Osmotic minipumps delivered 200p.g/day o f recombinant growth hormone for 4 weeks. Significances are shown for SLOB animals compared to normal animal following the same treatm ent procedure (S=sham, GH=GH-treated; *p<0.05, **p<0.01).
(a) l . Oi Spleen w eight T * * * ûb 0.5- 0.25- S GH SLOB S GH NORMAL
(b)
Soleus muscle weight
T
T
S GH NORMAL
(c) 0.4i
Kidney weight
S GH SLOB
S GH NORMAL
Figure 5.3 Effect of GH treatm enton organ weights in SLOB and normal male rats. Organ weights taken after 4 weeks treatment with 200gg/day of recombinant growth hormone. (S=sham, GH=GH-treated; ***p<0.001, n=6).
Chapter 5________________________________ Manipulation o f the SLOB Rat Phenotype
For this study I felt it was important to choose a moderate elevation in fat-content in the high-fat fed SLOB and normal animal groups. Many researchers simply wanting to assess the maximum effect of feeding a diet of very high fat content choose diets containing between 40-65% fat (Gong et al, 1990; Van-Heek et al, 1997). My aim o f high fat feeding SLOB rats was not really to increase fat intake to an absolute maximum, but more to alter the dietary composition to a more representative western human diet and observe how SLOB rats differ in their ability to respond to this challenge compared to normal rats. Laboratory animals at the NIMR are fed a standard chow diet consisting of 4% fat. To be more representative o f the average western human diet, a diet consisting o f 30% fat was selected for this study. It is also important to note that although fat and carbohydrate content differed in the two diets, protein content was kept the same to ensure effects of high fat feeding in SLOB rats were directly due to the macronutrient fat and not to protein.
10 0-day old rats were used and prior to the study all animals had been fed the normal chow diet. The reason I chose this age of animals was two-fold. First, the high fat diet would he made available prior to obvious obesity was apparent in terms o f gross body composition in both male and female SLOB rats. In this way, I could determine the influence of diet on the development of obesity rather than simply its maintenance or exacerbation. Second, growing rats are known to be in a dynamic state o f fat accumulation (Hirsch & Han 1969). I thought that the influence of dietary fat would therefore be more evident around this period. Separate male and female studies were conducted, each contained 4 groups of age-matched littermates (n=7). These groups consisted o f (a) normal rats fed standard chow (4% fat), (b) normal rats fed high-fat (30% fat), (c) SLOB rats fed standard chow (4% fat) and (d) SLOB rats fed high fat (30% fat).
In addition, I also included dwarf rats in these experiments to serve as controls for the effects o f GH-deficiency, since this is also present in SLOB rats. Thus, each experiment contained two additional groups of animals (n=5), (e) dwarf rats fed standard chow (4% fat) and (f) dwarf rats fed high fat (30% fat).
Animals were placed into individual metabolic cages, and allowed to acclimatise for 3-4 days before the start of the experiment. After switching food to 30% fat diet in
Chapter 5_________________________________Manipulation o f the SLOB Rat Phenotype
half the groups, food intakes and bodyweights were recorded at the same time each day for two weeks. Thereafter, animals were transferred to Bowman cages in groups of 5-7, with the same test diet and bodyweights recorded daily for a further 2 weeks.
5.3.1 Effect of high fat feeding in male rats
Usually, severe obesity in SLOB males is not evident until after 200 days o f age, however, on an enriched (30%) fat diet, gross obesity rapidly became evident, even at this earlier age (Figure 5.4 (a)). Animals on the high fat diet gained more weight compared to chow fed animals of the same type (Figure 5.4 (b)), however, high-fat fed SLOB males gained over twice the weight compared to high-fat fed normal littermates or dwarf rats. A change to a higher dietary fat content would normally result in a decrease in food intake which may or may not fully compensate for calorie intake (Horvath et a l, 2000). As SLOB rats gained excessive weight on a high fat diet, it was possible these animals were therefore consuming more calories than normal animals on a high fat diet. Figure 5.5 shows SLOB animals on a high fat diet did not significantly reduce their cumulative food intake whereas normal and dw arf
rats did, this may in part explain the increased weight gain in SLOB rats. The large increase in body weight change was also reflected in plasma leptin levels (Figure 5.6) and fat pad weights (Figure 5.7 (a), (b)). Leptin levels were significantly increased in SLOB and <7war/high fat fed animals but not in normal animals. High fat fed SLOB animals showed a significant increase in plasma leptins compared to high fat fed normal animals. All high-fat fed animals showed a significant increase in supra renal fat pad weight and again, high fat fed SLOB rats had larger supra renal fat pads compared to high fat fed normal animals. Results for testicular fat pad weights showed, high fat fed SLOB and normal animals had significantly greater fat pad weight compared to chow fed animals of the same type. However, high fat fed dw arf
rats did not show a significant increase in testicular fat pad weight. Also testicular fat pads in high fat fed SLOB rats did not weigh significantly more than in high-fat fed normal animals. Thus, from the observations made, high-fat feeding in SLOB males
(a) B o d y w eig h t chart 475 4 5 0 - 4 2 5 - 4 0 0 - 3 7 5 - 3 3 5 0 - w) 3 2 5 - 'p 3 0 0 - 2 7 5 - 2 5 0 - 2 2 5 - 2 0 0- 175- 150-1
fat diet administered on day 4