Effect of dietary fat and aging on adipose tissue cellularity in mice differing in genetic predisposition to obesity.

A line of mice had been developed which became obese when fed a commercial mouse breeder chow. This obese line was compared to a non-obese line at various ages to determine whether the type or amount of dietary fat would affect adipocyte size and number. Experimental diets containing beef tallow (38% of calories as beef fat and 2% as corn oil), corn oil (40% corn oil) or low fat (2% corn oil) were provided ad libitum at the time of weaning. Dorsoscapular subcutaneous fat pads were removed at 5, 6, 7, and 8 weeks and at 3, 6, 9, 12, 15, 18, and 21 months of age. Adipocyte size and number were determined histologically. Obese mice had enhanced adipocyte hyperplasia compared to the non-obese line. Only when eating the low fat diet did the obese mice have life-long elevated hypertrophy compared with their non-obese counterparts since non-obese mice responded to high fat feeding with a dramatic increase in adipocyte volume, regardless of type of fat. Body weight was greater in the obese line at all ages studied; however, some overlap in body weight was encountered between non-obese mice fed the high fat diets and genetically obese mice. Non-obese mice fed the low fat diet were smaller than mice in all other treatment groups throughout the study. Weight of the dorsoscapular subcutaneous adipose tissue was consistently greater in the obese line; however, high fat feeding greatly increased fat pad weight in non-obese mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Body weight and longevity in genetically obese and non-obese mice fed fat-modified diets.

Polygenically obese and genetically related non-obese male mice were fed ad libitum purified diets differing in quantity or type of fat from weaning onward to determine effects upon weight gain and life span. Non-obese mice lived 71% longer than mice in the obese line (mean = 753 d versus 441 d). Obese mice fed a low-fat diet containing 1% corn oil by weight lived 26% longer than their obese counterparts fed high fat diets containing 20% additional fat as either corn oil or beef tallow. The low fat diet had more of a normalizing effect upon longevity than upon body weight in polygenically obese mice. Conversely, dietary fat concentration had little effect upon longevity in non-obese mice and more effect upon body weight than in genetically obese mice. Type of dietary fat had little effect upon body weight and no effect upon longevity. The results of this study suggest that life span was only partially explained by body weight, and furthermore, that genetics play a greater role than body weight or dietary fat concentration in determining life span.

Effects of diet composition and fasting on glucose turnover in lean and polygenic obese mice.

Effects of high beef tallow (BT), high corn oil (CO) or low-fat (LF) diets upon the outcome of genetic obesity were investigated. Diets were instituted ad libitum at the time of weaning. When mice were six months of age, blood samples were taken 1, 5, 15, 30, and 60 minutes after intravenous injection of glucose-U-14C. Within dietary treatments, obese and lean mice showed similar plasma glucose-U-14C disappearance patterns. Plasma glucose disappearance always tended to be faster in ad libitum-fed mice relative to 24-hour fasted mice. Body glucose pool sizes tended to be larger in fed obese BT and LF mice compared to their lean counterparts. This pattern was not seen in non-fasted CO mice. Fasting caused a decrease in body glucose pool sizes in all mice. In contrast to CO and LF mice, lean BT mice appeared to conserve glucose during fasting the same as the obese line. Since the glucose disappearance curves can be described by a two-exponential decay function, at least a two-component or two-pool system must be involved in plasma glucose turnover. Calculated rate constants were used to express interchanges of carbon molecules between the glucose and glycogen pool and the net movement of glucose carbon to a carbon pool representing "irreversible end products". The data indicate that differences in glucose metabolism, in part, explain the possibility that dietary energy source can overcome the genetic tendency to leanness.

Animals as an energy source in third world agriculture.

Agricultural development programs have so far been largely unable to meet the food needs of the world's poorest. Increased food production can be achieved only from more intensive agriculture, which requires greater energy inputs per farm worker. Problems of technological infrastructure and escalating oil prices appear to preclude the spread of mechanization to Third World agriculture at this time. Efficient utilization of grazing animals in specific integrated farming systems could not only increase energy inputs through draft and transportation but also increase the yield of high-grade products and by-products from the renewable energy of biomass. An approach to development based on animal agriculture systems is suggested that might initiate a self-sustaining, more productive agriculture requiring only small inputs of fossil-fuel energy.

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples.

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.

A biochemical explanation for the fatty liver and kidney syndrome of broilers: its alleviation by the short-term use of dietary fat.

1. Fatty livers and kidney syndrome (FLKS) was induced in young broiler chickens by giving them a diet composed principally of wheat and meat meal. 2. FLKS resulted in reduced growth and increased liver weight; fasting for 18 h increased mortality, liver lipid and the specific activity of hepatic ATP-citrate lyase compared with birds fed on a commercial diet. The specific activities of hepatic fructose-1,6-diphosphate-1-phosphohydrolase and pyruvate carboxylase were reduced in birds suffering from FLKS and fasted for 18 h. 3. Feeding of the FLKS-inducing diet supplemented with 150 g animal tallow/kg for 54 h considerably reduced mortality while restoring liver composition and enzyme activities towards those observed in birds fed a commercial diet. Investigations indicated that the glycerol component of the fat was not responsible for the observed responses. 4. The present results suggest that in FLKS insufficiencies of biotin are induced in specific enzyme systems, but the syndrome may be alleviated without the use of supplementary biotin. 5. The evidence indicates that, when stressed, birds affected by FLKS diet from the hypoglycaemia occurring as a result of a reduced capacity for gluconeogenesis.

Increased permeability of the capillaries of the rat heart to plasma albumin with asphyxiation and with perfusion.

1. Studies on the rate of efflux from the isolated perfused rat heart of plasma albumin conjugated with Evans Blue showed the conjugate to have penetrated extensively the extravascular compartment of the organ during a period of 2 min. This was confirmed by direct analysis of hearts for Evans Blue after perfusion.2. Exposure of the hearts to Evans Blue-albumin conjugate for 8 min in vivo showed no significant penetration of the interstitial space.3. With the isolated preparation inclusion of promethazine in the perfusing medium significantly diminished the rate of penetration of the extravascular compartment by the conjugate as did injection of the animals with either reserpine 2 days before, or bretylium immediately before the experiment.4. Penetration of the interstitial compartment in vivo could be induced by repeated asphyxiation. This penetration could also be diminished by promethazine but was not influenced by mepyramine maleate. The increased permeability of capillaries to plasma proteins can be readily demonstrated in the whole animal by detecting the leakage from the vasculature of the plasma proteins conjugated with a dye (Menkin & Menkin, 1930; Miles & Miles, 1952). Evans Blue, which has been widely used as a vascular marker because of the stability of its conjugate with plasma albumin, is the most suitable dye for this purpose. In the present work this method has been applied to the isolated rat heart, to determine if changes in capillary permeability occur in the perfused tissue. When plasma albumin conjugated with Evans Blue was used as a vascular marker in this preparation, its rate of clearance was very much less than that of erythrocytes, and the amount contained in the heart corresponded to a space approaching that occupied by extracellular markers such as raffinose and inulin. It was concluded, therefore, that there was a failure of a considerable number of the cardiac capillaries to retain the plasma albumin, and subsequent work was directed towards the identification of the condition that gives rise to these changes and the possible involvement of a permeability factor.A preliminary account of part of this work was given to the Physiologcal Society (Sutherland & Young, 1961).