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ENHANSEMENT
OF IMMUNE RESPONSE |
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Clinica Medica, University of Trieste,
Ospedale Cattinara, Strada di Fiume 447, 34100 Trieste,
Italy.
The study aimed at determining,
in lean tissues from nonobese rats, whether physiological
hyperleptinemia with leptin-induced reduced caloric intake
and/or calorie restriction (CR) per se: 1) enhance mitochondrial-energy
metabolism gene transcript levels and oxidative capacity;
and 2) reduce triglyceride content. Liver and skeletal
muscles were collected from 6-month-old Fischer 344 rats
after 1-wk leptin sc infusion (0.4 mg/kg . d: leptin +
approximately 3-fold leptinemia vs. ad libitum-fed control)
or moderate CR (-26% of those fed ad libitum) in pair-fed
animals (CR). After 1 wk: 1) leptin and CR comparably
enhanced transcriptional expression of mixed muscle mitochondrial
genes (P < 0.05 vs. control); 2) CR independently increased
(P < 0.05 vs. leptin-control) hepatic mitochondrial-lipooxidative
gene expression and oxidative capacity; 3) hepatic but
not muscle mitochondrial effects of CR were associated
(P < 0.01) with increased activated insulin signaling
at AKT level (P < 0.05 vs. leptin-control); 4) liver
and muscle triglyceride content were comparable in all
groups. In additional experiments, assessing time course
of posttranscriptional CR effects, 3-wk superimposable
CR (P < 0.05): 1) increased both liver and muscle mitochondrial
oxidative capacity; and 2) selectively reduced muscle
triglyceride content. Thus, in nonobese adult rat: 1)
moderate CR induces early increments of mitochondrial-lipooxidative
gene expression and time-dependent increments of oxidative
capacity in liver and mixed muscle; 2) sustained moderate
CR alters tissue lipid distribution reducing muscle but
not liver triglycerides; 3) mitochondrial-lipid metabolism
changes are tissue-specifically associated with hepatic
AKT activation; 4) short-term physiological hyperleptinemia
has no independent stimulatory effects on muscle and liver
mitochondrial-lipooxidative gene expression. Increased
lean tissue oxidative capacity could favor substrate oxidation
over storage during reduced nutrient availability.
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Department of Medicine, Division of
Clinical Immunology, University of Texas Health Science
Center at San Antonio, San Antonio, TX 78229-3900, USA.
We compared the effects of calorie
restriction (CR) and cyclophosphamide (CTX) on the progression
of lupus nephritis and immunological changes in NZB/NZW
F1 mice. Ad libitum (AL)/CTX and CR delayed onset of proteinuria
and significantly decreased serum levels of anti-dsDNA,
anti-histone, and circulating immune complex antibodies.
CTX and CR prevented the increase in and activation of
B cells, the decline in CD8(+) T cells, and maintained
a higher proportion of naive CD4(+) and CD8(+) cells.
MHC class I antigen and LFA-1 expression on CD8(+) T cells
and MHC class II antigen on B cells were also decreased.
AL/CTX and CR prevented the increase in production of
IL-10 and up-regulated IL-2 production in T cells ex vivo.
We concluded that both CR and CTX can delay the onset
of autoimmune disease, in part by maintaining higher numbers
of naive T cells and the immune responsiveness of T cells
and decreasing the proportion of B cells.
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Nutritional Immunology Laboratory,
Jean Mayer USDA Human Nutrition Research Center on Aging,
Tufts University, 711 Washington Street, Boston, MA 02111,
USA.
OBJECTIVE: The immunologic effects
of isocaloric reduced- and low-fat diets and a voluntary
calorie-restricted low-fat diet resulting in weight loss
were compared to the immunologic effects of an average
American diet in hyperlipidemic individuals. METHODS:
Ten hyperlipidemic subjects were studied during three
six-week weight maintenance phases: baseline (BL) [35%
fat [14% saturated fat (SFA), 13% monounsaturated fat
(MUFA), 8% polyunsaturated fat (PUFA)] and 147 mg cholesterol
(C)/1000 kcal], reduced-fat (RF) [26% fat (4% SFA, 11%
MUFA, 11% PUFA) and 45 mg C/1000 kcal], and low-fat (LF)
[15% fat (5% SFA, 5% MUFA, 3% PUFA) and 35 mg C/1000 kcal]
diets followed by 12-week, low-fat calorie reduced phase
(LFCR). RESULTS: During the last phase, the subjects'
weight significantly decreased (p = 0.005). Cholesterol
levels were significantly reduced during all phases, compared
to BL diet (p < 0.05). Delayed-type hypersensitivity
(DTH) was assessed using Multi-test CMI. Maximum induration
diameters were 22.7, 25.4, 30.5, 34.5 mm for BL, RF, LF
and LFCR diets, respectively. Subjects on the LFCR diets
had significantly higher DTH compared to the BL diet (p
= 0.005). No significant effect of diet was observed on
lymphocyte proliferation or interleukin (IL)-1, IL-2 and
prostaglandin (PG) E(2) production. CONCLUSIONS: These
data suggest that low-fat diets (15% energy), under conditions
which result in weight loss, do not compromise and may
enhance the immune response of middle-aged and elderly
hyperlipidemic subjects. The results of this study provide
support for the hypothesis that moderate caloric restriction
in humans may have a beneficial effect on cell-mediated
immunity such as those reported in calorie-restricted
rodents.
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Department of Psychosomatic Medicine,
Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Although the total number of lymphocytes
decreased during fasting, NK cell activity increased significantly.
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