Prolactin (PRL) has recently been found to play a role in lipid metabolism in addition to its traditional roles in lactation and reproduction. However, the effects of PRL on lipid metabolism in liver and adipose tissues are unclear. Therefore, we aimed to study the role of PRL on lipid metabolism in goats. Twenty healthy eleven-month-old Yanshan cashmere goats with similar body weights (BWs) were selected and randomly divided into a control (CON) group and a bromocriptine (BCR, a PRL inhibitor, 0.06 mg/kg, BW) group. The experiment lasted for 30 days. Blood was collected on the day before BCR treatment (day 0) and on the 15th and 30th days after BCR treatment (days 15 and 30). On day 30 of treatment, all goats were slaughtered to collect their liver, subcutaneous adipose, and perirenal adipose tissues. A portion of all collected tissues was stored in 4% paraformaldehyde for histological observation, and another portion was immediately stored in liquid nitrogen for RNA extraction. The PRL inhibition had inconclusive effects found on BW and average daily feed intake (ADFI) in goats (
p > 0.05). PRL inhibition decreased the hormone-sensitive lipase (HSL) levels on day 30 (
p < 0.05), but the effects were inconclusive on days 0 and 15. PRL inhibition had inconclusive effects found on total cholesterol (TCH), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and acetyl-CoA carboxylase (ACC) on days 0, 15, and 30 (
p > 0.05). Furthermore, hematoxylin–eosin (HE) staining of the liver, subcutaneous adipose, and perirenal adipose sections showed that PRL inhibition had inconclusive effects on the pathological changes in their histomorphology (
p > 0.05), but measuring adipocytes showed that the area of perirenal adipocytes decreased in the BCR group (
p < 0.05). The qPCR results showed that PRL inhibition increased the expression of
PRL, long-form PRL receptor
(LPRLR), and short-form PRL receptor
(SPRLR) genes, as well as the expression of genes related to lipid metabolism, including sterol regulatory element binding transcription factor 1 (
SREBF1); sterol regulatory element binding transcription factor 2 (
SREBF2); acetyl-CoA carboxylase alpha (
ACACA); fatty acid synthase (
FASN); 3-hydroxy-3-methylglutaryl-CoA reductase (
HMGCR); 7-dehydrocholesterol reductase (
DHCR7); peroxisome proliferator-activated receptor gamma (
PPARG); and lipase E, hormone-sensitive type (
LIPE) in the liver (
p < 0.05). In the subcutaneous adipose tissue, PRL inhibition increased
SPRLR gene expression (
p < 0.05) and decreased the expression of genes related to lipid metabolism, including
SREBF1, SREBF2, ACACA, PPARG, and
LIPE (
p < 0.05). In the perirenal adipose tissue, the inhibition of PRL decreased the expression of the
PRL,
SREBF2, and
HMGCR genes (
p < 0.05). In conclusion, the inhibition of PRL decreases the serum HSL levels in cashmere goats; the effects of PRL on lipid metabolism are different in different tissues; and PRL affects lipid metabolic activity by regulating different PRLRs in liver and subcutaneous adipose tissues, as well as by decreasing the expression of the
PRL, SREBF2, and
HMGCR genes in perirenal adipose tissue.
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