Aubie Angel

Dietary fish oils limit adipose tissue hypertrophy in rats.

Total body mass, fat pad mass, and fat cell size were examined after feeding rats diets containing 20% triglycerides from fish oil or lard. Although food consumption, weight gain, and fat balance on the two diets were similar, lard-fed rats had 77% more fat in perirenal fat pads and 51% more fat in epididymal fat pads compared with fish oil-fed rats. There was no difference between the two groups in fat cell number in each region; however, adipocytes were significantly smaller in fish oil-fed rats. Thus dietary fish oil appears to limit triglyceride accumulation in adipose tissue and thereby limit fat cell trophic growth.

Effects of massive obesity on insulin sensitivity and insulin clearance and the metabolic response to insulin as assessed by the euglycemic clamp technique

Insulin sensitivity was studied in nine nondiabetic massively obese patients (one male and eight females ages 39.0 +/- 2.7 years, body mass index 47.1 +/- 1) by the euglycemic clamp technique (40 microU/m2/min) and compared to seven lean control subjects (three males and three females, ages 34.8 +/- 2.5 years, body mass index 23 +/- 1.1). Fasting plasma glucose, immunoreactive insulin, and C-peptide concentrations were higher in the massively obese patients than in the controls (P less than 0.025). Following exogenous insulin infusion, immunoreactive glucagon and C-peptide concentrations decreased similarly in the massively obese patients and controls, indicating normal sensitivity of the alpha and beta cell to insulin. Glucose uptake (M) expressed either as mg X min-1 of fat free mass was significantly reduced in the massively obese patients compared to the controls (P less than 0.001). Similarly, the M/I ratio (glucose uptake per unit of insulin) was significantly reduced in the massively obese patients (P less than 0.001). Free fatty acids and glycerol concentrations measured in the fasting state were significantly elevated in the massively obese patients (free fatty acids 678 +/- 51 v 467 +/- 55 mumol/L, P less than 0.05; glycerol 97 +/- 9 v 59 +/- 11 mumol/L, P less than 0.02). The effects of insulin on antilipolysis was assessed by measuring the reductions in free fatty acids and glycerol concentration during the glucose clamp study. Although the absolute levels remained higher in the massively obese patients, inhibition of lipolysis was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of hypothyroidism, age, and nutrition on LDL catabolism in the rat

Abstract To determine the effects of thyroid deficiency on LDL metabolism and degradation, the plasma clearance of 125I-LDL was determined in normal rats and rats fed chow containing propylthiouracil (PTU) 0.1% w/w and KI 0.16 gm 1 in the drinking water. After two weeks, T4 levels were significantly lower in the PTU groups compared to controls and plasma LDL cholesterol increased from 17.5 ± 1.2 ∗ ∗ Results given as mean ± SEM. mg 100 ml in controls to 32.5 ± 3.0 mg 100 ml in the hypothyroid animals. Human 125I-LDL (d 1.019–1.045) was injected intravenously under light anesthesia and tail tip blood was sampled repeatedly over 33–100 hr periods. In a semi-log plot the curve of 125I-LDL clearance described a log-linear profile suggesting a two-pool model. Compartmental analysis according to Matthews revealed two exponential curves, an initial rapid phase representing equilibration with an extravascular compartment (exponential 2), and a later slow phase of irreversible degradation (exponential 1). There was a marked delay in clearance of 125I-LDL in the hypothyroid rats as the slope of exponential 1 was 0.043 ± 0.001 ( t 1 2 = 16.2 hr ) versus 0.065 ± 0.002 ( t 1 2 = 10.7 hr ) in controls (P

Free fatty acid and ATP levels in adipocytes during lipolysis

Abstract Lipolytic hormones such as catecholamines and ACTH as well as lipolytic agents—e.g., 3′–5′ dibutyryl-cyclic AMP and methyl xanthines—are known to reduce ATP levels in adipose cells incubated in vitro. Considerable indirect evidence exists implicating intracellular FFA accumulation as a causative factor. To obtain more direct evidence for a causal relationship a simple and accurate method was developed for measuring intracellular FFA levels in isolated adipocytes using sucrose-U- 14 C as an extracellular marker. Following incubation, medium and cells were separated by centrifugation and the infranatant medium was removed by aspiration. The volume of medium trapped between cells was determined by measuring the amount of sucrose- 14 C retained in the packed adipose cell float. In this way the FFA content of the adipose cell float could be corrected for contamination by FFA bound to extracellular albumin. The basal FFA content of isolated adipocytes obtained from normal fed rats was 0.6 μEq./Gm. cell lipid. Addition of norepinephrine resulted in a rapid increase in intracellular FFA which plateaued at-22.5 μEq./Gm. cell lipid within 15 mins. Under optimal conditions of linear release of fatty acids—i.e., when medium albumin is not saturated by FFA—adipocyte ATP levels were not significantly depressed. Reduction of adipocyte ATP levels by lipolytic hormones correlated inversely with intracellular accumulation of FFA. Under these circumstances medium albumin approached saturation and intracellular FFA levels reached 6–9 μEq./Gm. cell lipid. Glucose, which is known to have a protective effect against ATP reduction, also prevented intracellular accumulation of FFA to cytotoxic levels. These results strongly support the view that the fall in adipocyte ATP after treatment with lipolytic hormone is the result of intracellular FFA accumulation, which depresses ATP synthesis by uncoupling oxidative phosphorylation. It is suggested that experiments undertaken to examine the relationship between effects of lipolytic hormones and other energy requiring processes must employ optimal in-vitro conditions—e.g., linear FFA release and nonsaturation of medium albumin—so as to prevent artifactual phenomena arising secondary to excessive intracellular FFA accumulation or ATP deficiency.

Weight loss in massive obesity: Reciprocal changes in plasma HDL cholesterol and HDL binding to human adipocyte plasma membranes☆

Human obesity is frequently associated with elevated plasma triglyceride and cholesterol concentrations and reduced high density lipoprotein (HDL) cholesterol, abnormalities that commonly revert to normal levels with weight loss. This study was undertaken to examine possible mechanism(s) associated with the changes in plasma HDL cholesterol concentrations in massively obese patients after weight loss. Ten massively obese patients (two men and eight women, age = 37.8 +/- 2.4 years) were studied before, during, and after 1 year of weight loss and weight maintenance following gastric stapling. Total cholesterol and low density lipoprotein cholesterol were within the normal range for sex and age before weight loss and did not change significantly during or after weight reduction. In the females, HDL cholesterol concentrations increased from 0.96 +/- 0.06 mmol/L to 1.23 +/- 0.3 mmol/L (mean +/- SEM, n = 8, P less than .05) with weight reduction. In the two men, plasma HDL cholesterol concentrations were, respectively, 1.22 and 0.65 mmol/L before and 1.23 and 0.98 mmol/L after weight loss. Specific binding of 125I-HDL2 and 125I-HDL3 to purified plasma membranes was determined using abdominal and omental fat depot before and after weight loss in six of the ten obese patients. An average reduction of 30% to 40% in 125I-HDL2 and 125I-HDL3 binding capacity to these membranes occurred after weight loss. Furthermore, a positive correlation (r = .65, n = 10, P less than .05) was observed between plasma HDL cholesterol and triglyceride concentrations before weight loss but not after weight loss (r = .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid structure of rat adipocyte plasma membranes following dietary lard and fish oil

We have determined the changes in the lipid structure of the adipocyte plasma membranes of rats receiving lard or fish oil in their diet. For this purpose, mature Wistar rats were fed 20% (w/w) lard or fish oil diets for 22 days, when the plasma membranes of the epididymal and perirenal adipocytes were prepared. Detailed analysis of the membrane lipids by chromatographic methods showed that dietary fat exerted a major effect on the lipid class and molecular species composition of the phospholipids. As a result of fish oil feeding, significant increases in the 20:5(n-3), 22:5(n-3) and 22:6(n-3) were detected in all glycerophospholipid classes, while the 18:1(n-9) and 18:2(n-6) and to a lesser extent 20:4(n-6) decreased. Incorporation of n-3 fatty acids increased the phosphatidylcholine/sphingomyelin ratio without changing the total phospholipid or free cholesterol content of the membrane. Fish oil feeding also caused a marked increase in the proportion of 24:1 in sphingomyelins, which occurred mainly at the expense of 18:0 and 24:0. New n-3 fatty acid-containing species appeared in the choline and ethanolamine glycerophospholipids, when compared to membrane lipids from lard-fed rats. Membranes from fish oil fed rats also had moderately higher levels of ether lipids. Few differences were seen between the membranes of the epididymal and perirenal adipocytes. It is concluded that dietary fish oils modify the lipid structure of rat adipocyte plasma membranes by increasing the ratio of phosphatidylcholine to sphingomyelin and by increasing the proportion of molecular species with polyunsaturated fatty acids, which would be anticipated to increase the fluidity of the lipid bilayer of adipocyte plasma membranes.

Brown Adipose Cells: Spontancous Mobilization of Endogenously Synthesized Lipid

Isolated brown adipose cell devoid of a basement membrane, readily synthesized a variety of lipids from radioctive acetate, a reactionaugmented by glucose and insulin. A large proportion of the newly formed fatty acids passed into the incubation medium. In intact brown adipose slices and isolated white adipose cells, most of the synthesized lipid was retained as glyceride esters. The date suggest that the rapid turnover of endogenously synthesized lipid in brown adipose cells is almost totally obscured in studies with intact tissue slices because of interstitial barriers to the egress of fatty acid.