The melanocortin action is biased toward protection from weight loss in mice.

The melanocortin action is well perceived for its ability to regulate body weight bidirectionally with its gain of function reducing body weight and loss of function promoting obesity. However, this notion cannot explain the difficulty in identifying effective therapeutics toward treating general obesity via activation of the melanocortin action. Here, we provide evidence that altered melanocortin action is only able to cause one-directional obesity development. We demonstrate that chronic inhibition of arcuate neurons expressing proopiomelanocortin (POMC) or paraventricular hypothalamic neurons expressing melanocortin receptor 4 (MC4R) causes massive obesity. However, chronic activation of these neuronal populations failed to reduce body weight. Furthermore, gain of function of the melanocortin action through overexpression of MC4R, POMC or its derived peptides had little effect on obesity prevention or reversal. These results reveal a bias of the melanocortin action towards protection of weight loss and provide a neural basis behind the well-known, but mechanistically ill-defined, predisposition to obesity development.

A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia.

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin's rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin's rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are both restored by leptin, whereas nutrient deprivation reverses the leptin action. Our results identify aberrant activation of LepRArc neurons owing to energy deprivation as the neural basis for T1D hyperglycemia and that leptin action is mediated by inhibiting LepRArc neurons through reversing energy deprivation.

Limit feeding as a strategy to increase energy efficiency in intensified cow-calf production systems.

Two experiments were conducted to measure efficiency of energy use in limit-fed cows. In Exp. 1, 32 pregnant, crossbred cows were used to examine the effects of dietary energy concentration and intake level on energy utilization and digestion. In a 2 × 2 factorial treatment arrangement, cows received diets formulated at either 1.54 Mcal NEm/kg high energy (H) or 1.08 Mcal NEm/kg low energy (L); amounts of each diet were fed at amounts to achieve either 80% (80) or 120% (120) of maintenance energy requirements. Fecal grab samples were collected on days 14, 28, 42, and 56 for determination of energy digestion and metabolizable energy (ME) intake. Acid detergent insoluble ash and bomb calorimetry were used to estimate fecal energy production. Cow body weight and 12th rib fat thickness were used to estimate body energy, using 8 different methods, at the beginning and end of a 56-d feeding period. Energy retention (RE) was calculated as the difference in body energy on days 0 and 56. Heat energy (HE) was calculated as the difference in ME intake and RE. Energy digestion increased (P = 0.04) with intake restriction. Cows consuming H tended to have greater (P = 0.08) empty body weight (EBW) gain than cows consuming L, but no difference was observed (P = 0.12) between cows fed 120 compared with cows fed 80. Estimates of HE were greater for L than H (P < 0.01) and greater for 120 than 80 (P < 0.01), such that estimated fasting heat production of H (57.2 kcal/kg EBW0.75) was lower than that of L (73.3 kcal/kg EBW0.75). In Exp. 2, 16 ruminally cannulated, crossbred steers were used to examine the effects of dietary energy concentration and intake level on energy digestion. Treatment arrangement and laboratory methods were replicated from Exp. 1. Following a 14-d adaptation period, fecal samples were collected, such that samples were represented in 2-h intervals post-feeding across 24 h. Diet × intake interactions were observed for nutrient digestibility. Energy digestibility was greater in steers fed H than in steers fed L (P < 0.01); however, digestibility of each nutrient increased by approximately 10% in steers fed H80 vs. those fed H120 (P ≤ 0.03); nutrient digestibility was similar among levels of intake in steers fed L (P = 0.54). These results suggest that intake restriction may increase diet utilization and that the magnitude of change may be related to diet energy density.