Involvement of plasma leptin in the voluntary feed intake regulation and body fat deposition in cattle

Professorial Chair Lecture

President Elpidio Quirino Professorial Chair Lecture

Place

Animal Science Lecture Hall

Date

11-15-2007

Abstract

Foremost of this work was the validation of bovine plasma leptin measurement using the multi-species leptin RIA kit (MSLK) with recombinant bovine leptin (rbleptin) as standard (chapter 2). The result showed 4.9 ng/ml rbleptin sensitivity and 11.2% cross-reactivity of MSLK antibody to standard rbleptin. Since the range of plasma leptin observed in the age- related changes (from 54 to 695 kg) was 5 to 58.4 ng/ml, the measurement of plasma leptin of bovine in all the experiment utilizing MSLK is justified. The 11.2% cross-reactivity revealed that the true plasma leptin concentration of bovine is underestimated by about 11% if recombinant human leptin was not replaced by rbleptin as standard.

The essence of this professorial lecture was focused on leptin's three areas of interests namely; (1) factors contributing to the changes in plasma leptin, (2) involvement of plasma leptin in feed intake regulation and (3) plasma leptin's possible role in the defense of body weight reduction or feed/energetic efficiency at different feeding systems and compensatory growth period.

1. Factors Involved in Plasma Leptin

Elevation in Beef Cattle

Consistently significant relationship between plasma leptin and body weight was observed in age-related plasma leptin profile (chapter 2), relationship of backfat thickness and plasma leptin (chapter 4), and the differences in plasma leptin of purebred and backcrossed Hereford (chapter 3). Similar significant relationship between plasma leptin and body weight was observed in male and female subjects (Moller, 1998) as well as backfat measures in sheep (Blache et al, 2000a; Ehrhardt et al, 2000). Clearly plasma leptin has become a good indicator of body fatness in animals.

Plasma leptin and IGF-1 profiles from early growing to late finishing stages of Holstein steers revealed significant concave and convex curvilinear relationship. The leveling-off of plasma IGF-1 and increase in plasma leptin from 13.5 to 27.4 monthly ages may imply indirect involvement of plasma IGF-1 in the stimulation of leptin released from adipose tissues. The increase in plasma leptin suggested possible parallel increase in body fat at this period.

The highly grain-fed (90%) Holstein steers from 16 to 23 monthly ages (chapter 4). revealed significant positive relationship between backfat thickness (BFT) and plasma leptin. Likewise, plasma leptin was significantly associated to plasma insulin, showing plasma leptin mimic of plasma insulin concentration from 16 to 23 months. The plasma leptin follow- through on plasma insulin may indicate occurrence of tissue insulin resistance with increase in adiposity (Olefsky et al, 1975, Vernon et al, 1985; Saad et al, 1998) and the involvement of insulin in the glucose utilization of adipose tissues causing plasma leptin increase. The persistence of plasma leptin mimic on plasma insulin may further be explained by the blunting of relative tissue insulin resistance due to progressive increase in endogenous insulin. The result of this experiment substantiated the assumed elevation of plasma leptin with backfat thickness in chapter 2. Furthermore it is proposed that plasma insulin elevation plays a role in plasma leptin increase of finishing Holstein steers offered high grain feed.

The effects of series of insulin injection (iv) on plasma glucose and plasma leptin was conceptualized due to previous result that plasma leptin mimic plasma insulin concentration in Holstein steers. Eight times a day insulin injection at 2 h interval resulted in plasma glucose depression of growing steers, and 11:45, 15.45 and 23:45 of finishing steers. In growing steers plasma leptin concentration was not significantly elevated, whereas in finishing steers significant plasma leptin elevation was observed at 11:45 and 15:45 The depression of plasma glucose in growing compared to finishing steers indicates relative tissue sensitivity of younger steers to insulin injection. The elevation of plasma leptin only in finishing steers and the corresponding 25% reduction in short-term TDN intake supports the necessary elevation of plasma leptin to cause feed intake reduction.

The relationship of plasma leptin and insulin concentration purebred (P<0.6581) and backcrossed (P<0.6224) Hereford in a year round grazing and feedlot fattening did not show significant relationship. This may imply disruption in the relationship of plasma leptin and insulin with low concentrate feeding. The shift from grazing to feedlot fattening resulted to sudden and significant elevation in plasma insulin of both breeds indicating the influence of concentrate feed on plasma insulin elevation. Also the shift from grazing to feedlot fattening showed sudden elevation of plasma leptin in purebred, but not in backcrossed Hereford. Apparently, there seems to be breed-related differences in the simultaneous elevation of plasma leptin and plasma insulin, which may be explained by the breed's ability to accumulate body fat.

Briefly, all the experiments revealed that the factors involved in plasma leptin elevation are (1) age-related body fat accumulation; (2) breed-related ability to accumulated body fat, (3) high grain feeding which cause plasma leptin to mimic plasma insulin and (4) fat tissues sensitivity to insulin action for lipid synthesis.

2. Plasma Leptin and Feed Intake Regulation in Beef Cattle

There are several evidences in the involvement of fat tissues in regulating feed intake and body weight in experimental animals. Kennedy (1953) reported the involvement of fat depot in rats and Coleman (1969) in his parabiotically joined obese-diabetic mice and normal mice resulted to loss in weight, hypoglycemia, and death of normal partner due to starvation. The injection of acid ethanol extracted from rat adipose tissues resulted to feed inhibition of mice (Goodner, 1996). The cloning of obesity gene and the expression of 146 peptide protein called leptin set a landmark in understanding obesity and regulation of feed intake in mouse (Zang et al, 1994). Plasma leptin and cerebrospinal leptin concentration increases with level of feeding in sheep (Blache et al, 2000a) and central administration (i.c.v.) of leptin resulted in feed intake reduction of well-fed ewes (Morrison, 2001) and male sheep (Blache et al, 2000b). These observations tempted us to study the effect of age- related increase in plasma leptin to TDN intake per kg BW for seven months fattening period. Also to study the effect of insulin injection on plasma leptin and TDN intake in growing and finishing steer.

The inter-relationship of BFT, plasma leptin and TDN intake, in 7 months period of finishing Holstein steers, revealed significant positive relationship between backfat thickness and plasma leptin. On the other hand significant negative relationship of TDN intake to plasma leptin and backfat thickness was observed. The reduction of TDN intake from 16 to 23 months was 0.38% TDN/kg BW (1.59 to 1.21%) or 25% of the initial month of TON consumption. This inter-relationship between backfat thickness, plasma leptin and TDN intake experiment can not conclude that backfat release of plasma leptin influenced TDN consumption per kg BW because exogenous leptin was not infused in the animals. Different levels of feeding with infusion of leptin are still needed to clearly understand the effect of leptin on feed intake. Hence, the results merely indicate that there is high possible involvement of body fat and plasma leptin in the feed intake reduction.

Since plasma leptin mimicked plasma insulin concentration from 16 to 23 months (Chapter 4), and that the physiological dose of insulin (6 mU/kg BW) caused feed intake reduction in sheep (Deetz and Wangsness, 1980, Deetz and Wangsness, 1981). The follow- up study was designed to know the effect of series of insulin injection (6 mU/kg BW) on plasma leptin and TDN intake per kg BW in growing and finishing Holstein steers. In growing steers plasma glucose was depressed while in finishing steers plasma glucose depression was observed only at limited interval. On the other hand plasma leptin was not significantly elevated in growing steers, whereas in finishing steers significant plasma leptin elevation was observed at 11.45 and 15:45. Generally, significant plasma leptin elevation was observed between 11:45 to 19:45, and at this period short-term feed consumption was measured as well in 24 h feed consumption. Insulin injection caused 25% reduction in short-term TDN intake of finishing steers, whereas in growing steers about 5% short-term TDN reduction (P<0.07) was measured. Both growing and finishing steers did not show reduction in 24 hour feed intake. Over-all results support the participation of plasma leptin in the insulin-induced feed intake reduction only in finishing Holstein steers.

3. Defense on Body Weight Gain Reduction or Feed Efficiency in Beef Cattle

The body weight susceptibility and resistance when offered high fat diet and offered low fat diets was observed in rats (Levin and Kessey, 1998) and mouse (Frederich, 1995, West, 1992), respectively. In domestic animals, this condition of body weight set point is measured on the basis of animals performance at a given nutrition or environmental condition. There has been no reported mechanism involved in the regulation of body weight set point in animals, and leptin may play a role but it may not be the principal regulator, because the general obesity in man is associated with high plasma leptin concentration. The studies on differences in performance and plasma leptin of purebred and backcrossed Hereford (chapter 3) and the changes in plasma leptin during compensatory growth highlight the body weight resistance under condition of low feeding status.

Ravussin reported (1997) that the relatively low plasma leptin concentration precedes weight gain in Pima Indians. This observation has something to do with the level of plasma leptin during weight maintenance of obese individuals. In this study, the involvement of leptin in the defense of body weight gain reduction can be highlighted in the higher ADG obtained by purebred relative to backcrossed Hereford when the steers were shifted from feedlot to grazing. During grazing, the purebred Hereford exhibited increase in plasma NEFA and attenuation of plasma leptin reflecting mobilization of body fat for lean tissue protein accretion. Grazing is a condition of lower plane of nutrition (relative to feedlot) and less fat deposition The feed or DM efficiency cannot be determined in this study because feed intake was not measured when the animals were on pasture. Energetic efficiency has been hypothesized to be the reason for the attenuation of plasma leptin, elevation of plasma NEFA and ability to posses higher ADG during grazing or condition of low feeding status in purebred Hereford. Leptin has been thought to be involved in energy metabolism in mouse (Campfield, 1996) and it was reported to have correlation with total energy expenditure in 5-year old children (Salbe, 1997). Furthermore plasma leptin has been thought to influence thyroid stimulating hormone (TSH) indirectly by activating the Agouti Related Protein (AGrP) (Flier et al, 2000). This has been supported by in vivo study in rats showing that AGrP acting as an antagonist to Melanocyte Stimulating Hormone (MSH) in enhancing the elevation of plasma TSH (Kim et al, 2000). Thyroid hormone is known as indicator of energy expenditure and the concentration in the blood is low during period of starvation (Kim et al, 2000), similar to plasma leptin in sheep undergoing low feed intake (Blache et al, 2000a).

Compensatory growth is a good condition for understanding energy, DM or gain efficiency. Because compensatory growth is a physiological process of accelerated growth in animals after experiencing feed reduction or significant body weight loss. In one year old steer this is characterized by favorable lean tissue accretion relative to body fat (Smith et al. 1972; Burton, 1974; Mader, 1989; Rompala, 1986) and improved DM efficiency or higher gain efficiency (Coleman and Evans, 1986; Adalla et al, 1988; Hornick, 1998; Hayden, 1993, Hicks et al, 1990).

The result of the changes in plasma leptin and IGF-1 during compensatory growth of steers (Chapter 6) resulted to depression of both hormones together with PUN and elevation of NEFA at the first 2 months of compensatory growth period. This condition can be attributed to fat mobilization and utilization of urea nitrogen in the blood for lean accretion. The level of plasma IGF-1 at early compensatory growth period of realimenting (REAL) steers was within 20 to 35 ng/ml, which was significantly lower compared to control steers and normal steers at 16.9 months old of chapter 2 (48 to 50 ng/ml). The down regulation of IGF-1 of REAL steers can be attributed to its active lean tissue growth.

Plasma leptin may not primarily regulate energetic efficiency, as the 'thrifty gene' that is assumed to primarily regulate energetic efficiency is about to be discovered by Dr. Ravussin in his work with the Pima Indians. These native of America has a characteristic of depositing excessive body fat despite similar quantity and quality of food consumed by ordinary man. Now they are trying to isolate and identify the so called "thrifty" gene. Leptin may not be the primary regulator of energy expenditure, however leptin may play a role in the mechanism involved in energetic efficiency, which is interesting and beneficial for livestock industry.

As a summary, plasma leptin attenuation, elevation of plasma NEFA, PUN depression and downregulation of IGF-1, represent a condition of fat substrate mobilization favoring lean deposition at early compensatory growth. Lowered plasma leptin may also reflect lower total energy expenditure resulting to energetic efficiency during catch-up growth.

Location

UPLB Main Library Special Collections Section (USCS)

College

College of Agriculture and Food Science (CAFS)

Language

English

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