The following is an abstract of the article discussed in the subsequent letter:
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ABSTRACT |
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Watson, Patricia M., Scott P. Commins, Rudolph J. Beiler, Heather
C. Hatcher, and Thomas W. Gettys. Differential regulation of leptin expression and function in A/J vs.
C57BL/6J mice during diet-induced obesity. Am J Physiol
Endocrinol Metab 279: E356-E365, 2000.Obesity-resistant (A/J) and obesity-prone (C57BL/6J) mice were weaned onto low-fat (LF) or high-fat (HF) diets and studied after
2, 10, and 16 wk. Despite consuming the same amount of food, A/J mice
on the HF diet deposited less carcass lipid and gained less weight than
C57BL/6J mice over the course of the study. Leptin mRNA was increased
in white adipose tissue (WAT) in both strains on the HF diet but to
significantly higher levels in A/J compared with C57BL/6J mice.
Uncoupling protein 1 (UCP1) and UCP2 mRNA were induced by the HF diet
in brown adipose tissue (BAT) and WAT of A/J mice, respectively, but
not in C57BL/6J mice. UCP1 mRNA was also significantly higher in
retroperitoneal WAT of A/J compared with C57BL/6J mice. The ability of
A/J mice to resist diet-induced obesity is associated with a
strain-specific increase in leptin, UCP1, and UCP2 expression in
adipose tissue. The findings indicate that the HF diet does not
compromise leptin-dependent regulation of adipocyte gene expression in
A/J mice and suggest that maintenance of leptin responsiveness confers
resistance to diet-induced obesity.
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LETTER |
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Revisiting Lessons from the C57BL/6J Mouse
To the Editor: We were delighted to see the article by Watson et al. on "Differential regulation of leptin expression and function in A/J vs. C57BL/6J mice during diet-induced obesity" that was recently published in the American Journal of Physiology (AJP; Am J Physiol Endocrinol Metab 279: E356-E365, 2000). The work presents a comprehensive replication of work done in our laboratories over the past 12 years on these strains of mice (1-8). Replication of previously published results is always welcome, although it is rare that journals such as AJP devote such significant space to it. We were definitely pleased to see that Watson et al. were able to reproduce our findings so precisely, but we were somewhat surprised that much of what was presented in this paper seemed to ignore that almost all of these findings are already in the literature, some for over a decade. The finding that high-fat feeding differentially affects ob gene expression in A/J and B6 mice is novel. As the authors noted, this result is not surprising, because it has previously been reported that plasma leptin levels differ in A/J and B6 mice on high-fat diets (7), and there is ample evidence that levels of ob gene expression in adipose tissue are reflected in serum levels. ![]() |
REFERENCES |
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Surwit, RS,
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Surwit, RS,
Petro AE,
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and
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Surwit, RS,
Wang S,
Petro AE,
Sanchis D,
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and
Collins S.
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9.
Watson, PM,
Commins SP,
Beiler RJ,
Hatcher HC,
and
Gettys TW.
Differential regulation of leptin expression and function in A/J vs. C57BL/6J mice during diet-induced obesity.
Am J Physiol Endocrinol Metab
279:
E356-E365,
2000
Richard S. Surwit, Sheila Collins, Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham, NC 27710 |
To the Editor: The studies reported in our recent
article (6) were motivated by the pioneering work of Drs.
Surwit and Collins in the area of dietary obesity. In particular, we
wanted to explore the mechanism underlying their recent observation
that high-fat diets induce a short-lived but larger than predicted increase in serum leptin in obesity-resistant compared with
obesity-prone mice (see Fig. 3D of Ref. 5). This involved
replicating their experimental design, and at the behest of the
referees, we provided basic observations about growth, fat deposition,
food intake, and serum profiles to demonstrate that there was a common
basis for comparing our findings with those published by the authors. We were particularly interested in the effect of high-fat diets on
leptin expression, and found that leptin mRNA was significantly higher
in obesity-resistant compared with obesity-prone mice at all time
points during the study (Table 2 of Ref. 6). This differs from Surwit
et al., who found that, after 6 wk on the high-fat diet, serum leptin
in obesity-resistant mice was either similar to or lower than levels in
obesity-prone mice. On the basis of our recent work showing that leptin
inhibits its own expression through central modulation of sympathetic
tone (1,2), we tested the hypothesis that differences in
inhibitory regulation were responsible for diet-induced differences in
leptin expression between the mouse strains. This was done by acutely
treating mice of each strain with a selective
REPLY
3-adrenergic receptor agonist after various times on the
high-fat diet and evaluating the ability of the agonist to downregulate
leptin mRNA. We found significant differences in the way leptin was
regulated between the strains (Fig. 3 of Ref. 6) that were unrelated to
any change in
3-adrenergic receptor expression or
function in white adipose tissue. These findings are novel and likely
related to observations from others showing that transcriptional
regulation of gene expression by
-agonists differs in adipocytes
from A/J and C57BL/6J mice (3, 4). The challenge that lies
ahead will be in defining the molecular basis for this difference and
relating it to the relative propensity of mice from these two strains
to become obese. The studies of Drs. Surwit and Collins have led the
way in demonstrating the utility of this model system for studying
diet-induced obesity and defining the role of the adipocyte in the process.
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REFERENCES |
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1.
Commins, SP,
Marsh DJ,
Thomas SA,
Watson PM,
Padgett MA,
Palmiter RD,
and
Gettys TW.
Norepinephrine is required for leptin effects on gene expression in brown and white adipose tissue.
Endocrinology
140:
4772-4776,
1999
2.
Commins, SP,
Watson PM,
Levin N,
Beiler RJ,
and
Gettys TW.
Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different -adrenoceptor subtypes.
J Biol Chem
275:
33059-33067,
2000
3.
Guerra, C,
Koza RA,
Yamashita H,
Walsh K,
and
Kozak LP.
Emergence of brown adipocytes in white fat in mice is under genetic controlEffects on body weight and adiposity.
J Clin Invest
102:
412-420,
1998
4.
Koza RA, Hohmann SM, Guerra C, Rossmeisl M, and Kozak LP.
Synergistic gene interactions control the induction of the
mitochondrial uncoupling protein (UCP1) gene in white fat tissue.
J Biol Chem 275: 34486-34492.
5.
Surwit, RS,
Petro AE,
Parekh P,
and
Collins S.
Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mice.
Diabetes
46:
1516-1520,
1997[Abstract].
6.
Watson, PM,
Commins SP,
Beiler RJ,
Hatcher HC,
and
Gettys TW.
Differential regulation of leptin release and function in A/J versus C57BL/6J mice during diet-induced obesity.
Am J Physiol Endocrinol Metab
279:
E356-E365,
2000
Thomas W. Gettys, Departments of Medicine and Biochemistry and Molecular Biology Medical University of South Carolina Charleston, SC 29425 |