Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mice

Diabetes ◽  
1997 ◽  
Vol 46 (9) ◽  
pp. 1516-1520 ◽  
Author(s):  
R. S. Surwit ◽  
A. E. Petro ◽  
P. Parekh ◽  
S. Collins
Diabetes ◽  
1997 ◽  
Vol 46 (9) ◽  
pp. 1516-1520 ◽  
Author(s):  
R. S. Surwit ◽  
A. E. Petro ◽  
P. Parekh ◽  
S. Collins

1997 ◽  
Vol 273 (1) ◽  
pp. R113-R120 ◽  
Author(s):  
B. Ahren ◽  
S. Mansson ◽  
R. L. Gingerich ◽  
P. J. Havel

Mechanisms regulating circulating leptin are incompletely understood. We developed a radioimmunoassay for mouse leptin to examine the influence of age, dietary fat content, and fasting on plasma concentrations of leptin in the background strain for the ob/ob mouse, the C57BL/6J mouse. Plasma leptin increased with age [5.3 +/- 0.6 ng/ml at 2 mo (n = 23) vs. 14.2 +/- 1.6 ng/ml at 11 mo (n = 15), P < 0.001]. Across all age groups (2-11 mo, n = 160), log plasma leptin correlated with body weight (r = 0.68, P < 0.0001), plasma insulin (r = 0.38, P < 0.001), and amount of intra-abdominal fat (r = 0.90, P < 0.001), as revealed by magnetic resonance imaging. Plasma leptin was increased by a high-fat diet (58% fat for 10 mo) and reduced by fasting for 48 h. The reduction of plasma leptin was correlated with the reduction of plasma insulin (r = 0.43, P = 0.012) but not with the initial body weight or the change in body weight. Moreover, the reduction in plasma leptin by fasting was impaired by high-fat diet. Thus plasma leptin in C57BL/6J mice 1) increases with age or a high-fat diet; 2) correlates with body weight, fat content, and plasma insulin; and 3) is reduced during fasting by an action inhibited by high-fat diet and related to changes of plasma insulin.


1997 ◽  
Vol 82 (2) ◽  
pp. 561-565 ◽  
Author(s):  
David S. Weigle ◽  
P. Barton Duell ◽  
William E. Connor ◽  
Robert A. Steiner ◽  
Michael R. Soules ◽  
...  
Keyword(s):  

2020 ◽  
Vol 98 (12) ◽  
Author(s):  
Jose M Ramos-Nieves ◽  
Sarah L Giesy ◽  
Molly M McGuckin ◽  
Yves R Boisclair

Abstract Intrauterine growth restriction (IUGR) is often observed in one of the fetuses carried by well-fed prolific ewes. This condition is the result of an insufficient placental size to cover the nutritional needs of the fetus during the near exponential growth phase of the last trimester. After birth, these IUGR offspring have an elevated appetite and lower maintenance energy requirements, suggesting dysregulation of homeostatic systems governing energy metabolism. It is also unknown whether the consequent increase in fatness occurs similarly in both visceral and carcass fractions. To address these questions, lambs differing in birth size (BS, IUGR vs. Normal, 2.6 ± 0.05 vs. 4.2 ± 0.07 kg, P &lt; 0.001) were offered unlimited amounts of a low fat [LF; 22% of dry matter (DM)] or a high fat (HF; 38% of DM) milk replacer and slaughtered on day 14 of postnatal age (n = 7 to 8 for each BS × Diet); a second group of IUGR lambs (n = 3 for each diet) was slaughtered when they reached 8.5 kg, corresponding to the weight of Normal lambs on day 14. When normalized to body weight (BW), the DM and energy intake of IUGR lambs were higher than those of Normal lambs over the first 14 d of life (BS, P &lt; 0.01), but contrary to expectations, the HF diet did not exacerbate these effects of the IUGR condition. Intrauterine growth restricted lambs had increased viscera fat with both diets (BS and Diet, P &lt; 0.05) but increased carcass fat only with the LF diet (BS × Diet, P = 0.08); the fatness promoting effect of the IUGR condition was increased in both body fractions when lamb groups were compared at the fixed BW of 8.5 kg. A subset of metabolic hormones was analyzed, including the metabolic rate-setting hormone thyroxine (T4) and its possible positive regulator leptin. Plasma T4 was lower in IUGR than in Normal lambs at birth (P &lt; 0.05) but then disappeared by day 7 of postnatal life (BS × Day, P &lt; 0.01). On the other hand, the HF diet had no effect on plasma T4 over the first 3 d but caused an increase, irrespective of BS by day 11 (Diet × Day, P &lt; 0.001). Plasma leptin increased with dietary fat and time (P &lt; 0.06) but bore no relation to the effects of BS or Diet on plasma T4. These data show that IUGR and Normal lambs are similarly unable to adjust caloric intake in early life and that the fatness promoting effects of the IUGR condition are more pronounced in the viscera than in the carcass. These data also reveal dynamic regulation of plasma T4 by BS and Diet in neonatal lambs.


2003 ◽  
Vol 88 (4) ◽  
pp. 1577-1586 ◽  
Author(s):  
David S. Weigle ◽  
David E. Cummings ◽  
Patricia D. Newby ◽  
Patricia A. Breen ◽  
R. Scott Frayo ◽  
...  

Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 ± 57 vs. 580 ± 56 ng/ml·24 h; P = NS). Body weight decreased from 74.6 ± 2.4 to 70.8 ± 2.7 kg on the ad libitum 15% F diet (P &lt; 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Claus Brandt ◽  
Maria Pedersen ◽  
Anders Rinnov ◽  
Anne S. Andreasen ◽  
Kirsten Møller ◽  
...  

Background. Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes.In vitro, TNF-αinduces fstl3 secretion, which suggests a link to inflammation.Objective. To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans.Study Design. Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS), TNF-α, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans.Results. Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-αand IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans.Conclusion. Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-αincreased plasma fstl3, suggesting that TNF-αis one of the inflammatory drivers of increased systemic levels of fstl3.


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