The Leptin-Fat Ratio is Constant, and Leptin May be Part of Two Feedback Mechanisms for Maintaining the Body Fat Set Point in Non-Obese Male Fischer 344 Rats

Abstract

While plasma leptin and adiposity have been found to be strongly related, the specific nature of this relationship has yet to be clarified. Hence, plasma leptin and three indicators of adiposity were measured in adult male Fischer 344 rats on three different long-term diets: continuous ad libitum feeding; ad libitum feeding until early adulthood, then continuous 60% caloric restriction; and ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, then ad libitum feeding for 5 months. Body fat was found to be a good linear correlate of plasma leptin, with a zero Y-intercept, and a constant plasma leptin-body fat ratio. The number of adipocytes per rat and % body fat were strong quadratic correlates of plasma leptin. This study is the first to find a zero Y-intercept and constant plasma leptin-body fat ratio, probably because it is the first to simultaneously measure both plasma leptin and body fat accurately, and to account for confounders such as gender, genetic background, age, physical activity, and possibly obesity. The study also explored the effect of switching calorically-restricted rats to ad libitum feeding. This led to a rapid rise, and then synchronized up-down cycles in average daily food intake and body weight, with a steady upward trend toward a new stable body-weight set point. It is hypothesized that this pattern resulted from two simultaneous feedback mechanisms, possibly involving leptin. In conclusion, this study suggests that, under controlled conditions, the plasma leptin-body fat ratio is a constant for a particular mammalian strain, independent of dietary history.

Plasma and cerebrospinal fluid leptin levels are maintained despite enhanced food intake in progesterone-treated rats

“…Since its discovery a few years ago, serum leptin has proved to be directly related to body fat in both humans (1,2) and rats (3). This has been considered to be the main evidence that it is a white adipose tissue (WAT) messenger signalling the size of the fat store to the central nervous system, in agreement with the adipostatic theory proposed by Kennedy (4) and sustained by Hausberger's experiments (5).…”

Leptin immunoexpression and innervation in rat interscapular brown adipose tissue of cold-acclimated rats: the effects of L-arginine and L-NAME.

“…Leptin is a hormone whose plasma levels are directly related to the amount of body fat [41,42]. Leptin, therefore, informs the central nervous system of the fat store size, which is in agreement with the adipostatic theory proposed by Kennedy [43].…”

Dietary Soy Isoflavone–Aglycone Lowers Food Intake in Female Rats With and Without Ovariectomy

“…Greenberg et al . have suggested that, under controlled conditions, the plasma‐leptin‐to‐body‐fat ratio is constant for a particular mammalian strain, independent of dietary history (38). In this study, significant positive correlations were also observed between the serum leptin concentration and the sum of the fat tissue weights in male, female, and OVX rats ( , and ).…”