Quantitative trait loci for individual adipose depot weights in C57BL/6ByJ x 129P3/J F2 mice

To understand how genotype influences fat patterning and obesity, we conducted an autosomal genome scan using male and female F₂ hybrids between the C57BL/6ByJ and 129P3/J parental mouse strains. Mice were studied in middle-adulthood and were fed a low-energy, low-fat diet during their lifetime. We measured the weight of the retroperitoneal adipose depot (near the kidney) and the gonadal adipose depot (near the epididymis in males and ovaries in females). An important feature of the analysis was the comparison of linkage results for absolute adipose depot weight and depot weight adjusted for body size, i.e., relative weight. We detected 67 suggestive linkages for six phenotypes, which fell into one of three categories: those specific to absolute but not relative depot weight (Chr 5, 11, and 14), those specific to relative but not absolute depot weight (Chr 9, 15, and 16), and those involving both (Chr 2 and 7). Some quantitative trait loci (QTLs) affected one adipose depot more than another: Retroperitoneal depot weight was linked to Chr 8, 11, 12, and 17, but the linkage effects for the gonadal depot were stronger for Chr 5, 7, and 9. Several linkages were specific to sex; for instance, the absolute weight of gonadal fat was linked to Chromosome 7 in male (LOD = 3.4) but not female mice (LOD = 0.2). Refining obesity as a phenotype may uncover clues about gene function that will assist in positional cloning efforts.     

Quantitative trait Loci for regional adiposity in mouse lines divergently selected for food intake

Objective: Obesity is thought to result from an interaction between genotype and environment. Excessive adiposity is associated with a number of important comorbidities; however, the risk of obesity‐related disease varies with the distribution of fat throughout the body. The aim of this study was to map quantitative trait loci (QTLs) associated with regional fat depots in mouse lines divergently selected for food intake corrected for body mass. Research Methods and Procedures: Using an F₂ intercross design (n = 457), the dry mass of regional white (subcutaneous, gonadal, retroperitoneal, and mesenteric) adipose tissue (WAT) and brown adipose tissue (BAT) depots were analyzed to map QTLs. Results: The total variance explained by the mapped QTL varied between 12% and 39% for BAT and gonadal fat depots, respectively. Using the genome‐wide significance threshold, nine QTLs were associated with multiple fat depots. Chromosomes 4 and 19 were associated with WAT and BAT and chromosome 9 with WAT depots. Significant sex × QTL interactions were identified for gonadal fat on chromosomes 9, 16, and 19. The pattern of QTLs identified for the regional deposits showed the most similarity between retroperitoneal and gonadal fat, whereas BAT showed the least similarity to the WAT depots. Analysis of total fat mass explained in excess of 40% of total variance. Discussion: There was limited concordance between the QTLs mapped in our study and those reported previously. This is likely to reflect the unique nature of the mouse lines used. Results provide an insight into the genetic basis of regional fat distribution.     

Organization of white adipose tissue in lemuridae

The gross anatomy of white adipose tissue was studied in seven carcasses representing three lemurid species (Lemur catta, Eulemur fulvus, E. mongoz) to validate in vivo methods of assessing fatness, and to contribute to a comprehensive database on the organization of adipose tissue in Mammalia. During the years preceding their deaths, subjects had been either caged or semi-provisioned under semi-captive conditions, and their body masses had been recorded several times annually. All specimens were as fat or fatter than anthropoid primates maintained for long periods under comparable conditions. At least eight superficial, four intra-abdominal, and two intermuscular adipose depots were described, all of which were comparable to those described previously for macaques and humans. All typical mammalian depots were present. Many superficial depots adhered tightly to the skin and/or underlying muscles. The superficial “paunch” depot on the outer ventral wall of the abdomen, characteristic of anthropoid primates, was found in all specimens. The existence of this depot in lemurs suggests that it evolved early in Primates. As in monkeys and humans, the paunch was very variable in size, massive in obese specimens but almost absent in moderately lean ones, confirming that extensive accumulation and selective depletion of adipose tissue at this depot is a special feature of Primates. In some obese specimens, adipose tissue on the ventral and lateral thorax and on the inner dorsal wall of the abdomen, extending around the kidneys and into the pelvic canal, was also massive. The investigation allowed for improvement of protocols for external measurement in ongoing research on growth, mass, and fatness in ringtailed and redfronted lemurs. Comparisons of subjects' ranges of body mass change during adult life with masses of adipose tissue found upon dissection suggested that much of lemurs' predictable seasonal change in body mass is due to changes in the mass of white adipose tissue. © 1995 Wiley-Liss, Inc.     

Two blood pressure/cardiac mass quantitative trait loci on Chromosome 3 in Dahl rats

Interval mapping was used to identify putative quantitative trait loci (QTL) for blood pressure and cardiac mass on Chromosome (Chr) 3 in F₁(S × R) × S population of 150 rats raised on an 8% NaCl diet. Two genetic markers 95.7 cM apart, D3Wox3 and D3Mco5 (tightly linked to Edn3), showed ``suggestive' linkage to blood pressure (LOD = 2.0 and 1.8 respectively). In addition, D3Wox3 showed ``suggestive' linkage to heart weight (LOD = 2.5), and D3Mco5 showed ``suggestive' linkage to body weight–adjusted heart weight (LOD = 2.1). Congenic rats (designated S.R-Edn3) were constructed by introgressing the R-rat Edn3 allele (and flanking loci) into the S strain. On a 2% NaCl diet, S.R-Edn3 rats had lower blood pressure (21.4 mm Hg, P= 0.0005) and heart weight (59 mg, P= 0.0038) compared with S rats, confirming the existence of a blood pressure QTL on Chr 3 near Edn3 even though QTL linkage analysis of blood pressure did not achieve stringent statistical criteria for significance. The results of the congenic experiment and the large distance between the two putative QTL suggest the presence of at least two independent blood pressure/cardiac mass QTL detectable on Chr 3 in the Dahl rat model of genetic hypertension. Received: 24 April 1998 / Accepted: 29 September 1998     

Depot differences in steroid receptor expression in adipose tissue: possible role of the local steroid milieu

Sex hormones play an important role in adipose tissue metabolism by activating specific receptors that alter several steps of the lipolytic and lipogenic signal cascade in depot- and sex-dependent manners. However, studies focusing on steroid receptor status in adipose tissue are scarce. In the present study, we analyzed steroid content [testosterone (T), 17beta-estradiol (17beta-E2), and progesterone (P4)] and steroid receptor mRNA levels in different rat adipose tissue depots. As expected, T levels were higher in males than in females (P = 0.031), whereas the reverse trend was observed for P4 (P < 0.001). It is noteworthy that 17beta-E2 adipose tissue levels were higher in inguinal than in the rest of adipose tissues for both sexes, where no sex differences in 17beta-E2 tissue levels were noted (P = 0.010 for retroperitoneal, P = 0.005 for gonadal, P = 0.018 for mesenteric). Regarding steroid receptor levels, androgen (AR) and estrogen receptor (ER)alpha and ERbeta densities were more clearly dependent on adipose depot location than on sex, with visceral depots showing overall higher mRNA densities than their subcutaneous counterparts. Besides, expression of ERalpha predominated over ERbeta expression, and progesterone receptor (PR-B form and PR-A+B form) mRNAs were identically expressed regardless of anatomic depot and sex. In vitro studies in 3T3-L1 cells showed that 17beta-E2 increased ERalpha (P = 0.001) and AR expression (P = 0.001), indicating that estrogen can alter estrogenic and androgenic signaling in adipose tissue. The results highlighted in this study demonstrate important depot-dependent differences in the sensitivity of adipose tissues to sex hormones between visceral and subcutaneous depots that could be related to metabolic situations observed in response to sex hormones.     

Expressions of Leptin and Insulin‐Like Growth Factor‐I Are Highly Correlated and Region‐Specific in Adipose Tissue of Growing Rats

Objective: Anatomically distinct adipose tissue regions differ in their predominant modality of growth (i.e., cellular hypertrophy vs. hyperplasia). We examined site‐specific patterns of expression of two genes whose products, leptin and insulin‐like growth factor‐I (IGF‐I), could be involved in mediating differential growth and metabolism of white adipose tissue. We also related these patterns of expression to measures of adipose depot cellularity. Research Methods and Procedures: Male Wistar rats were fed ad libitum and studied from ages 7 weeks to ～12 months. Terminal measures of body weights; weights, composition, and cellularity of four white adipose depots; circulating leptin and IGF‐I; and adipose depot‐specific expression levels of leptin and IGF‐I were measured in subsets of rats at 7, 12, 22, 42, and 46 weeks of age. Results: Both leptin and IGF‐I mRNAs are quantitatively expressed in a depot‐specific manner, in the following order: retroperitoneal ? epididymal > mesenteric > subcutaneous inguinal. Furthermore, there is a marked correlation between the expressions of these hormones in the various regions of adipose tissue of rats during the first year of life. The mechanisms that underlie the parallel expressions of leptin and IGF‐I appear to be related to fat‐cell volume. Discussion: Because both leptin and IGF‐I have been implicated in the regulation of energy homeostasis and are both expressed in adipose tissue, the depot‐specific linkage between the two genes suggests interaction at the autocrine level. This interaction may have an important role in determining functional properties particular to individual adipose depots.     

Resistance to Aging-Associated Obesity in Capsaicin-Desensitized Rats One Year after Treatment

Previous studies demonstrated reduced weight of abdominal white adipose tissue depots and of carcass fat in capsaicin-desensitized (Cap-Des) rats up to 8 months after treatment. The objective of the present study was to find out whether aging-associated obesity and hyperplasia of retroperitoneal white adipose tissue was prevented in older (13.5 month old) Cap-Des rats, one year after treatment with Cap (done when they were 1.5 months old). The prevalence of obesity is known to increase in rats by this age. Abdominal white adipose tissue depots weighed less in old Cap-Des rats, both epididymal (9% less) and retroperitoneal (30% less). The number of mature white adipocytes was 28% less in the retroperitoneal depot but was not significantly different in the epididymal depot. Adipocyte size was not different. Carcass fat was less, both total and as percent of body weight. Food intake was normal for their reduced body size. The exponential increase in retroperitoneal white adipose tissue weight characteristic of aging rats that are becoming obese was virtually absent in Cap-Des rats. We conclude that lack of function of capsaicin-sensitive afferent autonomic nerves, known to be destroyed in Cap-Des rats, results in an alteration in energy balance conducive to leanness. We suggest that the attenuated age-associated increase in circulating CGRP (derived mainly from capsaicin-sensitive nerves) in the Cap-Des rat results in a lower degree of aging-associated insulin-resistance, hence in a lesser degree of obesity.     

Effect of high-fat diet feeding on leptin receptor expression in white adipose tissue in rats: depot- and sex-related differential response

Previous studies have illustrated the importance of leptin receptor (OB-Rb) mediated action on adipocytes in the regulation of body weight. The aim of the present study was to investigate in male and female rats the effects of high-fat (HF) diet feeding on the expression levels of OB-Rb in different depots of white adipose tissue (WAT), and its relation to fatty acid oxidation capacity. Male and female Wistar rats were fed until the age of 6 months with a normal-fat (NF) or non-isocaloric HF-diet (10 and 45% calories from fat, respectively). At this age, the weight of three different fat depots (retroperitoneal, mesenteric and inguinal) and the expression levels of OB-Rb, PPARα and CPT1 in these depots were measured. HF-diet feeding resulted in an increase in the weight of the different fat depots, the retroperitoneal depot being the one with the greatest increase in both sexes. In this depot, HF-diet feeding resulted in a significant decrease in OB-Rb mRNA levels, more marked in male than in female rats. In the mesenteric depot, the effects of HF-diet feeding on OB-Rb mRNA levels were sex-dependent: they decreased in males rats (associated with a decrease in PPARα and CPT1 mRNA levels), but increased in female rats. In the inguinal depot, OB-Rb expression was not affected by HF-diet feeding. These results show that a chronic intake of an HF-diet altered the expression of OB-Rb in WAT in a depot and sex-dependent manner. The decreased expression of OB-Rb in the internal depots of male rats under HF-diet feeding, with the resulting decrease in leptin sensitivity, can help to explain the higher tendency of males to suffer from obesity-linked disorders under HF-diet conditions.     

Genetic loci affecting body weight and fatness in a C57BL/6J × PWK/PhJ mouse intercross

To determine the genetic variation that contributes to body composition in the mouse, we interbred a wild-derived strain (PWK/PhJ; PWK) with a common laboratory strain (C57BL/6J; B6). The parental, F₁, and F₂ mice were phenotyped at 18 weeks old for body weight and composition using dual-energy X-ray absorptiometry (DEXA). A total of 479 (244 male and 235 female) F₂ mice were genotyped for 117 polymorphic markers spanning the autosomes. Twenty-eight suggestive or significant linkages for four traits (body weight, adjusted lean and fat weight, and percent fat) were detected. Of these, three QTLs were novel: one on the proximal portion of Chr 5 for body weight (Bwq8; LOD = 4.7), one on Chr 3 for lean weight (Bwtq13; LOD = 3.6), and one on Chr 11 for percent fat (Adip19; LOD = 5.8). The remaining QTLs overlapped previously identified linkages, e.g., Adip5 on Chr 9. One QTL was sex-specific (present in males only) and seven were sex-biased (more prominent in one sex than the other). Most alleles that increased body weight were contributed by the B6 strain, and most alleles that increased percent fat were contributed by the PWK strain. Eight pairs of interacting loci were identified, none of which exactly overlapped the main-effect QTLs. Many of the QTLs found in the B6 × PWK cross map to the location of previously reported linkages, suggesting that some QTLs are common to many strains (consensus QTLs), but three new QTLs appear to be particular to the PWK strain. The location and type of QTLs detected in this new cross will assist in future efforts to identify the genetic variation that determines the ratio of lean to fat weight as well as body size in mice.     

Cellularity of adipose depots in the genetically obese Zucker rat

Cell size and number of three adipose depots, epididymal, retroperitoneal, and subcutaneous, were determined during growth of the obese Zucker rat ("fatty") and nonobese Zucker control. Cellularity of these depots in the adult "fatty" was compared with that in nonobese controls and in nonobese Zucker rats made obese by ventromedial hypothalamic lesions. Epididymal and retroperitoneal depots in the nonobese rat grew by cell enlargement and increase in cell number until the 14th wk, when number became fixed; further increase in depot size occurred by cell enlargement. The subcutaneous depot added cells until the 26th wk. In the Zucker "fatty," cell number increased until the 26th wk in all depots, accompanied by extreme cell enlargement. The enlarged adipose depots of the adult Zucker "fatty," when compared with the nonobese control, are the result of both hypertrophy and hyperplasia. Depot enlargement in the lesioned animal is the result of hypertrophy. "Fatties" have more cells in adipose depots than do lesioned rats. Genetic obesity in the Zucker rat is clearly different from the obesity produced by hypothalamic lesioning.     

Metabolism of Different Adipose Tissues in Vivo in the Rat

To explore regional differences in triglyceride retention in white adipose tissues of growing male rats, the mass of adipocytes from epididymal, retroperitoneal, inguinal, and mesenteric tissues were followed with time. In order to attempt to explain regional differences, adipose tissue metabolism was studied in vivo and in vitro. (U-¹⁴ C) oleic acid in sesame oil was given by gastric gavage to conscious male and female rats, and accumulation and half-life of radioactivity measured. Lipoprotein lipase activity and lipolysis were studied in vitro. Adipocyte triglyceride mass increased linearly in all the depots during 4 months of observation. The increase in mass was more pronounced in retroperitoneal (0.31 μg) and epididymal (0.30 μg) than in mesenteric (0.11 μg) or inguinal (0.05 μg) adipocytes. In the fed state label from (U-¹⁴C) oleic acid first increased with time in liver, muscle, and adipose tissues. In the liver radioactivity peaked at 4 hours, and was not measurable in either liver or muscle after a time point between 24 hours to 1 week. In contrast label continued to increase in adipose tissues up to about 16 hours to 24 hours, suggesting transfer of label by recirculation from liver and muscle to adipose tissues. Thereafter the radioactivity decreased. When expressed per adipocyte uptake of label was not significantly different between white adipose tissues. The rate of decrease between 7 days and 4 months was, however, more rapid in mesenteric and inguinal than, particularly, epididymal, and, probably, retroperitoneal adipocytes. These results were partly parallel to in vitro data on lipoprotein lipase activity, which was not different between depots, and the rate of lipolysis, which was higher in mesenteric than other adipocytes. These results suggest that differences in weight increase of adipose tissue regions are due mainly to differences in the rate of mobilization of adipocyte triglycerides. When expressed per gram triglyceride, uptake and mobilization of label were clearly more rapid in mesenteric than other white adipose tissues. This is probably explained by a combination of a higher adipocyte density plus the metabolic characteristics of adipocytes in this depot. Since mesenteric adipose tissue is smaller than the other depots studied, the absolute contribution of this tissue to the energy supply of the body is probably not different from that of other adipose tissues, however. A large uptake and short half life was observed in interscapular adipose tissue. This region contains brown adipocytes, and the results therefore suggest that lipid uptake for thermogenic purposes is of a considerable magnitude. It was concluded that among white adipose tissues, the mesenteric tissue has a rapid turnover of triglyceride. This is probably due to a combination of a high density and specific metabolic characteristics of these adipocytes. Factors in the microenvironment of adipocytes probably contribute to the high turnover either directly, or by modification of cellular characteristics.     

Correlated responses in development and distribution of fat depots in mice selected for body composition traits

Summary Development of adipose tissue in five depots was investigated in mice selected for high or low 12-week epididymal fat pad weight as a percentage of body weight (HF and LF lines), or high or low 12-week hind carcass weight as a percentage of body weight (HL and LL lines). An unselected control line (RC) was maintained. Hind carcass (HC) and fat pads from subcutaneous hindlimb, subcutaneous forelimb, gonads, kidneys and mesentery were dissected and weighed at 4, 6, 9, 12 or 15 weeks of age. Generally, body weight (BW), daily gain (DG), feed intake (FI), feed efficiency (FE) and feed intake/metabolic body weight (FC) were higher (P0.05) in HF than in LF, and in LL than in HL. HF had more fat (as a percentage of BW) than LF in all depots (P-0.01), and asymmetry (P0.01) was detected for gonadal fat. LL consistently had a higher (P0.01) fat percentage than HL, and asymmetry (P0.01) was observed for perirenal fat. At age of selection, ranking of fat depot weights as a percentage of total fat depot weight was not changed by selection; however, gonadal fat accounted for more of the total fat in HF and LL compared with RC, while the opposite was found in LF and HL. HC percentage was higher (P0.01) in HL than LL, and higher (P0.01) in LF than HF. Growth rate of each fat depot relative to BW was not affected by selection. These results demonstrated that selection for proportion of fat in one depot or for HC percentage changed fat percentage in other depots. However, the rate of fat deposition in each depot relative to body weight gain was not altered.     

QTL for body composition on chromosome 7 detected using a chromosome substitution mouse strain

Objective: Previous studies in mice have detected quantitative trait loci (QTLs) on chromosome 7 that affect body composition. As a step toward identifying the responsible genes, we compared a chromosome 7 substitution strain C57BL/6J‐Chr7^129S1/SvImJ/Na (CSS‐7) to its host (C57BL/6J) strain. Methods and Procedures: Fourteen‐week‐old mice were measured for body size (weight, length), organ weight (brain, heart, liver, kidneys, and spleen), body and bone composition (fat and lean weight; bone area, mineral content, and density), and individual adipose depot weights (gonadal, retroperitoneal, mesenteric, inguinal, and subscapular). Differences between the CSS‐7 strain and the host strain were interpreted as evidence for the presence of one or more QTLs on chromosome 7. Results: Using this criterion, we detected QTLs for body weight, bone area, bone mineral content, brain, and heart weight, most adipose depot weights and some indices of fatness. A few strain differences were more pronounced in males (e.g., most adiposity measures) and others were more pronounced in females (e.g., bone area). QTLs for body length, lean weight, bone mineral density, and kidney, spleen, and liver weight were not detected. Discussion: This study found several associations that suggest one or more QTLs specific to the weight of select tissues and organs exist on mouse chromosome 7. Because these loci are detectable on a fixed and uniform genetic background, they are reasonable targets for high‐resolution mapping and gene identification using a congenic approach.     

Cellularity of adipose depots in six strains of genetically obese mice

Adipocyte cell size and number of three adipose depots, gonadal, subcutaneous, and retroperitoneal, were determined in several strains (aA(y), aA(iy), dbdb, obob, and NZO) of adult genetically obese mice, male and female, and in male gold thioglucose-treated mice. Epididymal pad cellularity was determined during development in yellow and viable yellow obese mice and their lean littermates, as well as in the NCS/R mouse. Cell number in the mouse epididymal pad in both lean and genetically obese animals is determined early in development, i.e., before weaning. Cell enlargement is the consistent and usually dominant morphological explanation for adipose depot enlargement in genetic and in gold thioglucose-induced mouse obesity. In some instances, hyperplasia accompanied the hypertrophy, occurring most often in the subcutaneous depot. Cell number in the subcutaneous pad of the obese-hyperglycemic female is four times that of the lean control and represents the most extreme case of hyperplasia observed. In fact, hyperplasia was consistently seen in the obob mouse. A classification for genetic obesity based primarily upon the cellularity characteristics of the adipose depots is proposed.     

Estrogen Reduces 11β‐Hydroxysteroid Dehydrogenase Type 1 in Liver and Visceral,but Not Subcutaneous,Adipose Tissue in Rats

Following menopause, body fat is redistributed from peripheral to central depots. This may be linked to the age related decrease in estrogen levels. We hypothesized that estrogen supplementation could counteract this fat redistribution through tissue‐specific modulation of glucocorticoid exposure. We measured fat depot masses and the expression and activity of the glucocorticoid‐activating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1) in fat and liver of ovariectomized female rats treated with or without 17β‐estradiol. 11βHSD1 converts inert cortisone, or 11‐dehydrocorticosterone in rats into active cortisol and corticosterone. Estradiol‐treated rats gained less weight and had significantly lower visceral adipose tissue weight than nontreated rats (P < 0.01); subcutaneous adipose weight was unaltered. In addition, 11βHSD1 activity/expression was downregulated in liver and visceral, but not subcutaneous, fat of estradiol‐treated rats (P < 0.001 for both). This downregulation altered the balance of 11βHSD1 expression and activity between adipose tissue depots, with higher levels in subcutaneous than visceral adipose tissue of estradiol‐treated animals (P < 0.05 for both), opposite the pattern in ovariectomized rats not treated with estradiol (P < 0.001 for mRNA expression). Thus, estrogen modulates fat distribution, at least in part, through effects on tissue‐specific glucocorticoid metabolism, suggesting that estrogen replacement therapy could influence obesity related morbidity in postmenopausal women.     

Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F₂ crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F₂ intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL.     

Quantitative trait locus analysis for obesity reveals multiple networks of interacting loci

Obesity is a highly heritable and genetically complex trait with hundreds of potential loci identified. An intercross of 513 F₂ progeny between the SM/J × NZB/BINJ inbred mouse strains was generated to identify quantitative trait loci (QTL) that are involved in the weight of four fat pads: mesenteric, inguinal, gonadal, and retroperitoneal. Sex and lean body weight were treated as covariates in the analysis of these fat pads. This analysis uncoupled genetic effects related to overall body size from those influencing the adiposity of a mouse. We identified multiple significant QTL. QTL alleles associated with increased lean body weight and individual fat pad weights are contributed by the NZB background. Adiposity loci are distinct from these body size QTLs and high-adiposity alleles are contributed by the SM background. An extended network of epistatic QTL is also observed. A QTL on Chr 19 is the center of a network of eight interacting QTL, Chr 4 is the center of six, and Chr 17 the center of four interacting QTL. We conclude that interacting networks of multiple genes characterize the regulation of fat pad depots and body weight. Haplotype patterns and a literature-driven approach were used to generate hypotheses regarding the identity of the genes and pathways underlying the QTL.